Catalyst recycle methods

ABSTRACT

The present invention provides novel solutions to the problem of recycling carbonylation catalysts in epoxide carbonylation processes. The inventive methods are characterized in that the catalyst is recovered in a form other than as active catalyst. In some embodiments, catalyst components are removed selectively from the carbonylation product stream in two or more processing steps. One or more of these separated catalyst components are then utilized to regenerate active catalyst which is utilized during another time interval to feed a continuous carbonylation reactor.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. patent application Ser. No.15/308,989, filed on Nov. 4, 2016, which is a U.S. National Phase patentapplication of PCT/US2015/028123, filed Apr. 29, 2015, which claims thebenefit of U.S. Provisional Patent Application Ser. No. 61/988,495,filed May 5, 2014, the disclosures of which are hereby incorporatedherein by reference in their entirety.

BACKGROUND OF THE INVENTION

The production of three- and four-carbon commodity chemicals such asacrylic acid (AA), butane diol (BDO), and tetrahydrofuran (THF) from lowpriced two-carbon feedstocks is of increasing interest. The appeal ofthe approach stems from the ability to substitute low costethane-derived feedstocks for the propylene and butane currently used inproduction of C3s and C4s respectively. The discovery and exploitationof huge shale gas reserves rich in ethane has made this approach evenmore compelling since ethane prices are falling while propylene priceshave tended to increase along with petroleum.

One particularly promising process in this vein relies on thecarbonylation of ethylene oxide to produce AA (via propiolactone orpolypropiolactone) or BDO and THF via succinic anhydride. A number ofcatalysts have been investigated for this process, the most active ofwhich are the carbonylation catalysts developed by Geoff Coates andcoworkers at Cornell University. The Coates catalysts are homogenouscatalysts combining a cationic Lewis acid and an anionic metal carbonyl.These catalysts demonstrate high product selectivity and relatively highrates as compared to prior catalysts such as those based on cobaltcarbonyls in combination with pyridine derivatives or neutral Lewisacids such as BF₃.

Nevertheless, a major challenge in commercializing ethylene oxidecarbonylation is the development of a viable continuous productionprocess. To be economical, the carbonylation catalyst must be capable ofturning over tens or hundreds of thousands of equivalents of epoxide. Toachieve such turnover numbers it is probable that an efficient catalystrecycle loop will be required. Several such processes have beendescribed including: removal of carbonylation product by distillationfrom a solution of catalyst in a high boiling solvent as described in WO2010/118128; selective retention of catalyst in the reactor bynanofiltration WO 2014/008232; separation of product from a catalystsolution by crystallization WO 2012/030619, and WO 2013/122905; andimmobilization of the catalyst on a solid support, WO/2013063191.

A key challenge is the tendency for the carbonylation catalyst todecompose in a CO-depleted atmosphere, and/or the propensity of themetal carbonyl portion of the catalyst to become disassociated fromother catalyst components such as a Lewis acid or heterocycle. Thepresent invention provides solutions to this and other related problems.

SUMMARY OF THE INVENTION

In a first aspect, the present invention provides novel solutions to theproblem of recycling carbonylation catalysts in epoxide carbonylationprocesses. In the broadest sense, the inventive methods aredifferentiated from prior art attempts to solve this problem by the factthat the inventive catalyst recycle regime does not occur in real-time.Whereas previous attempts to recycle the catalysts from epoxidecarbonylation processes have featured catalyst recycle loops where thecatalyst is retrieved from the reaction product stream in acatalytically active form which is continuously fed back to thecarbonylation reactor, the present methods are differentiated by thefact that the catalyst (or indeed inactive catalyst products orcomponents) are separated and accumulated over some interval of time andthen utilized in the carbonylation process at a later time. Theintervals of time over which the catalyst is accumulated typically rangefrom hours to days and are longer than the typical loop transport orprocessing times in existing processes which are normally on the orderof minutes.

In certain embodiments, the inventive methods are characterized in thatthe catalyst is recovered in a form other than as active catalyst. Insome embodiments, catalyst components are removed selectively from thecarbonylation product stream in two or more processing steps. One ormore of these separated catalyst components are then utilized toregenerate active catalyst which is utilized during another timeinterval to feed a continuous carbonylation reactor. For example, incertain embodiments a method such as ion exchange is used to selectivelyremove an ionic component of a carbonylation catalyst (for example thecationic Lewis acid) to the exclusion of other catalyst components (forexample an anionic metal carbonyl) which can be separated in a laterstep and accumulated separately to be re-used or disposed of.

One advantage of the present methods is elimination of costly equipmentand processes necessary to recover the active catalysts which aretypically oxygen sensitive, thermally unstable, unstable in theatmospheres lacking carbon monoxide, and in some cases reactive towardthe carbonylation products at elevated temperatures. By removing therequirement that the catalyst be recovered in active form, the presentinvention provides substantial advantages in terms of the complexity andcost of the catalyst recovery steps.

DEFINITIONS

Definitions of specific functional groups and chemical terms aredescribed in more detail below. For purposes of this invention, thechemical elements are identified in accordance with the Periodic Tableof the Elements, CAS version, Handbook of Chemistry and Physics, 75^(th)Ed., inside cover, and specific functional groups are generally definedas described therein. Additionally, general principles of organicchemistry, as well as specific functional moieties and reactivity, aredescribed in Organic Chemistry, Thomas Sorrell, University ScienceBooks, Sausalito, 1999; Smith and March March's Advanced OrganicChemistry, 5^(th) Edition, John Wiley & Sons, Inc., New York, 2001;Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., NewYork, 1989; Carruthers, Some Modern Methods of Organic Synthesis, 3^(rd)Edition, Cambridge University Press, Cambridge, 1987; the entirecontents of each of which are incorporated herein by reference.

Certain compounds of the present invention can comprise one or moreasymmetric centers, and thus can exist in various stereoisomeric forms,e.g., enantiomers and/or diastereomers. Thus, inventive compounds andcompositions thereof may be in the form of an individual enantiomer,diastereomer or geometric isomer, or may be in the form of a mixture ofstereoisomers. In certain embodiments, the compounds of the inventionare enantiopure compounds. In certain other embodiments, mixtures ofenantiomers or diastereomers are provided.

Furthermore, certain compounds, as described herein may have one or moredouble bonds that can exist as either a Z or E isomer, unless otherwiseindicated. The invention additionally encompasses the compounds asindividual isomers substantially free of other isomers andalternatively, as mixtures of various isomers, e.g., racemic mixtures ofenantiomers. In addition to the above-mentioned compounds per se, thisinvention also encompasses compositions comprising one or morecompounds.

As used herein, the term “isomers” includes any and all geometricisomers and stereoisomers. For example, “isomers” include cis- andtrans-isomers, E- and Z-isomers, R- and S-enantiomers, diastereomers,(D)-isomers, (L)-isomers, racemic mixtures thereof, and other mixturesthereof, as falling within the scope of the invention. For instance, acompound may, in some embodiments, be provided substantially free of oneor more corresponding stereoisomers, and may also be referred to as“stereochemically enriched.”

Where a particular enantiomer is preferred, it may, in some embodimentsbe provided substantially free of the opposite enantiomer, and may alsobe referred to as “optically enriched.” “Optically enriched,” as usedherein, means that the compound is made up of a significantly greaterproportion of one enantiomer. In certain embodiments the compound ismade up of at least about 90% by weight of an enantiomer. In someembodiments the compound is made up of at least about 95%, 97%, 98%,99%, 99.5%, 99.7%, 99.8%, or 99.9% by weight of an enantiomer. In someembodiments the enantiomeric excess of provided compounds is at leastabout 90%, 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9%. In someembodiments, enantiomers may be isolated from racemic mixtures by anymethod known to those skilled in the art, including chiral high pressureliquid chromatography (HPLC) and the formation and crystallization ofchiral salts or prepared by asymmetric syntheses. See, for example,Jacques, et al., Enantiomers, Racemates and Resolutions (WileyInterscience, New York, 1981); Wilen, S. H., et al., Tetrahedron 33:2725(1977); Eliel, E. L. Stereochemistry of Carbon Compounds (McGraw-Hill,NY, 1962); Wilen, S. H. Tables of Resolving Agents and OpticalResolutions p. 268 (E. L. Eliel, Ed., Univ. of Notre Dame Press, NotreDame, Ind. 1972).

The terms “halo” and “halogen” as used herein refer to an atom selectedfrom fluorine (fluoro, —F), chlorine (chloro, —Cl), bromine (bromo,—Br), and iodine (iodo, —I).

The term “aliphatic” or “aliphatic group”, as used herein, denotes ahydrocarbon moiety that may be straight-chain (i.e., unbranched),branched, or cyclic (including fused, bridging, and spiro-fusedpolycyclic) and may be completely saturated or may contain one or moreunits of unsaturation, but which is not aromatic. Unless otherwisespecified, aliphatic groups contain 1-30 carbon atoms. In certainembodiments, aliphatic groups contain 1-12 carbon atoms. In certainembodiments, aliphatic groups contain 1-8 carbon atoms. In certainembodiments, aliphatic groups contain 1-6 carbon atoms. In someembodiments, aliphatic groups contain 1-5 carbon atoms, in someembodiments, aliphatic groups contain 1-4 carbon atoms, in yet otherembodiments aliphatic groups contain 1-3 carbon atoms, and in yet otherembodiments aliphatic groups contain 1-2 carbon atoms. Suitablealiphatic groups include, but are not limited to, linear or branched,alkyl, alkenyl, and alkynyl groups, and hybrids thereof such as(cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

The term “heteroaliphatic,” as used herein, refers to aliphatic groupswherein one or more carbon atoms are independently replaced by one ormore atoms selected from the group consisting of oxygen, sulfur,nitrogen, phosphorus, or boron. In certain embodiments, one or twocarbon atoms are independently replaced by one or more of oxygen,sulfur, nitrogen, or phosphorus. Heteroaliphatic groups may besubstituted or unsubstituted, branched or unbranched, cyclic or acyclic,and include “heterocycle,” “hetercyclyl,” “heterocycloaliphatic,” or“heterocyclic” groups.

The term “epoxide”, as used herein, refers to a substituted orunsubstituted oxirane. Substituted oxiranes include monosubstitutedoxiranes, disubstituted oxiranes, trisubstituted oxiranes, andtetrasubstituted oxiranes. Such epoxides may be further optionallysubstituted as defined herein. In certain embodiments, epoxides comprisea single oxirane moiety. In certain embodiments, epoxides comprise twoor more oxirane moieties.

The term “glycidyl”, as used herein, refers to an oxirane substitutedwith a hydroxyl methyl group or a derivative thereof. The term glycidylas used herein is meant to include moieties having additionalsubstitution on one or more of the carbon atoms of the oxirane ring oron the methylene group of the hydroxymethyl moiety, examples of suchsubstitution may include, but are not limited to: alkyl groups, halogenatoms, aryl groups etc. The terms glycidyl ester, glycidyl acrylate,glydidyl ether etc. denote substitution at the oxygen atom of theabove-mentioned hydroxymethyl group, i.e. that oxygen atom is bonded toan acyl group, an acrylate group, or an alkyl group respectively.

The term “acrylate” or “acrylates” as used herein refer to any acylgroup having a vinyl group adjacent to the acyl carbonyl. The termsencompass mono-, di- and tri-substituted vinyl groups. Examples ofacrylates include, but are not limited to: acrylate, methacrylate,ethacrylate, cinnamate (3-phenylacrylate), crotonate, tiglate, andsenecioate.

The term “polymer”, as used herein, refers to a molecule of highrelative molecular mass, the structure of which comprises the multiplerepetition of units derived, actually or conceptually, from molecules oflow relative molecular mass. In certain embodiments, a polymer iscomprised of only one monomer species (e.g., polyethylene oxide). Incertain embodiments, a polymer of the present invention is a copolymer,terpolymer, heteropolymer, block copolymer, or tapered heteropolymer ofone or more epoxides.

The term “unsaturated”, as used herein, means that a moiety has one ormore double or triple bonds.

The terms “cycloaliphatic”, “carbocycle”, or “carbocyclic”, used aloneor as part of a larger moiety, refer to a saturated or partiallyunsaturated cyclic aliphatic monocyclic, bicyclic, or polycyclic ringsystems, as described herein, having from 3 to 12 members, wherein thealiphatic ring system is optionally substituted as defined above anddescribed herein. Cycloaliphatic groups include, without limitation,cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl,cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, andcyclooctadienyl. In some embodiments, the cycloalkyl has 3-6 carbons.The terms “cycloaliphatic”, “carbocycle” or “carbocyclic” also includealiphatic rings that are fused to one or more aromatic or nonaromaticrings, such as decahydronaphthyl or tetrahydronaphthyl, where theradical or point of attachment is on the aliphatic ring. In someembodiments, a carbocyclic groups is bicyclic. In some embodiments, acarbocyclic group is tricyclic. In some embodiments, a carbocyclic groupis polycyclic.

The term “alkyl,” as used herein, refers to saturated, straight- orbranched-chain hydrocarbon radicals derived from an aliphatic moietycontaining between one and six carbon atoms by removal of a singlehydrogen atom. Unless otherwise specified, alkyl groups contain 1-12carbon atoms. In certain embodiments, alkyl groups contain 1-8 carbonatoms. In certain embodiments, alkyl groups contain 1-6 carbon atoms. Insome embodiments, alkyl groups contain 1-5 carbon atoms, in someembodiments, alkyl groups contain 1-4 carbon atoms, in yet otherembodiments alkyl groups contain 1-3 carbon atoms, and in yet otherembodiments alkyl groups contain 1-2 carbon atoms. Examples of alkylradicals include, but are not limited to, methyl, ethyl, n-propyl,isopropyl, n-butyl, iso-butyl, sec-butyl, sec-pentyl, iso-pentyl,tert-butyl, n-pentyl, neopentyl, n-hexyl, sec-hexyl, n-heptyl, n-octyl,n-decyl, n-undecyl, dodecyl, and the like.

The term “alkenyl,” as used herein, denotes a monovalent group derivedfrom a straight- or branched-chain aliphatic moiety having at least onecarbon-carbon double bond by the removal of a single hydrogen atom.Unless otherwise specified, alkenyl groups contain 2-12 carbon atoms. Incertain embodiments, alkenyl groups contain 2-8 carbon atoms. In certainembodiments, alkenyl groups contain 2-6 carbon atoms. In someembodiments, alkenyl groups contain 2-5 carbon atoms, in someembodiments, alkenyl groups contain 2-4 carbon atoms, in yet otherembodiments alkenyl groups contain 2-3 carbon atoms, and in yet otherembodiments alkenyl groups contain 2 carbon atoms. Alkenyl groupsinclude, for example, ethenyl, propenyl, butenyl, 1-methyl-2-buten-1yl,and the like.

The term “alkynyl,” as used herein, refers to a monovalent group derivedfrom a straight- or branched-chain aliphatic moiety having at least onecarbon-carbon triple bond by the removal of a single hydrogen atom.Unless otherwise specified, alkynyl groups contain 2-12 carbon atoms. Incertain embodiments, alkynyl groups contain 2-8 carbon atoms. In certainembodiments, alkynyl groups contain 2-6 carbon atoms. In someembodiments, alkynyl groups contain 2-5 carbon atoms, in someembodiments, alkynyl groups contain 2-4 carbon atoms, in yet otherembodiments alkynyl groups contain 2-3 carbon atoms, and in yet otherembodiments alkynyl groups contain 2 carbon atoms. Representativealkynyl groups include, but are not limited to, ethynyl, 2-propynyl(propargyl), 1-propynyl, and the like.

The term “carbocycle” and “carbocyclic ring” as used herein, refers tomonocyclic and polycyclic moieties wherein the rings contain only carbonatoms. Unless otherwise specified, carbocycles may be saturated,partially unsaturated or aromatic, and contain 3 to 20 carbon atoms.Representative carbocyles include cyclopropane, cyclobutane,cyclopentane, cyclohexane, bicyclo[2,2,1]heptane, norbornene, phenyl,cyclohexene, naphthalene, spiro[4.5]decane,

The term “aryl” used alone or as part of a larger moiety as in“aralkyl”, “aralkoxy”, or “aryloxyalkyl”, refers to monocyclic andpolycyclic ring systems having a total of five to 20 ring members,wherein at least one ring in the system is aromatic and wherein eachring in the system contains three to twelve ring members. The term“aryl” may be used interchangeably with the term “aryl ring”. In certainembodiments of the present invention, “aryl” refers to an aromatic ringsystem which includes, but is not limited to, phenyl, naphthyl,anthracyl and the like, which may bear one or more substituents. Alsoincluded within the scope of the term “aryl”, as it is used herein, is agroup in which an aromatic ring is fused to one or more additionalrings, such as benzofuranyl, indanyl, phthalimidyl, naphthimidyl,phenanthridinyl, or tetrahydronaphthyl, and the like.

The terms “heteroaryl” and “heteroar-”, used alone or as part of alarger moiety, e.g., “heteroaralkyl”, or “heteroaralkoxy”, refer togroups having 5 to 14 ring atoms, preferably 5, 6, 9 or 10 ring atoms;having 6, 10, or 14 π electrons shared in a cyclic array; and having, inaddition to carbon atoms, from one to five heteroatoms. The term“heteroatom” refers to nitrogen, oxygen, or sulfur, and includes anyoxidized form of nitrogen or sulfur, and any quaternized form of a basicnitrogen. Heteroaryl groups include, without limitation, thienyl,furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl,oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl,thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl,purinyl, naphthyridinyl, benzofuranyl and pteridinyl. The terms“heteroaryl” and “heteroar-”, as used herein, also include groups inwhich a heteroaromatic ring is fused to one or more aryl,cycloaliphatic, or heterocyclyl rings, where the radical or point ofattachment is on the heteroaromatic ring. Nonlimiting examples includeindolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl,indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl,cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl,carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl,tetrahydroquinolinyl, tetrahydroisoquinolinyl, andpyrido[2,3-b]-1,4-oxazin-3(4H)-one. A heteroaryl group may be mono- orbicyclic. The term “heteroaryl” may be used interchangeably with theterms “heteroaryl ring”, “heteroaryl group”, or “heteroaromatic”, any ofwhich terms include rings that are optionally substituted. The term“heteroaralkyl” refers to an alkyl group substituted by a heteroaryl,wherein the alkyl and heteroaryl portions independently are optionallysubstituted.

As used herein, the terms “heterocycle”, “heterocyclyl”, “heterocyclicradical”, and “heterocyclic ring” are used interchangeably and refer toa stable 5- to 7-membered monocyclic or 7- to 14-membered bicyclicheterocyclic moiety that is either saturated or partially unsaturated,and having, in addition to carbon atoms, one or more, preferably one tofour, heteroatoms, as defined above. When used in reference to a ringatom of a heterocycle, the term “nitrogen” includes a substitutednitrogen. As an example, in a saturated or partially unsaturated ringhaving 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, thenitrogen may be N (as in 3,4-dihydro-2H-pyrrolyl), NH (as inpyrrolidinyl), or ⁺NR (as in N-substituted pyrrolidinyl).

A heterocyclic ring can be attached to its pendant group at anyheteroatom or carbon atom that results in a stable structure and any ofthe ring atoms can be optionally substituted. Examples of such saturatedor partially unsaturated heterocyclic radicals include, withoutlimitation, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl,pyrrolidonyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl,tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl,dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl,and quinuclidinyl. The terms “heterocycle”, “heterocyclyl”,“heterocyclyl ring”, “heterocyclic group”, “heterocyclic moiety”, and“heterocyclic radical”, are used interchangeably herein, and alsoinclude groups in which a heterocyclyl ring is fused to one or morearyl, heteroaryl, or cycloaliphatic rings, such as indolinyl,3H-indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl, wherethe radical or point of attachment is on the heterocyclyl ring. Aheterocyclyl group may be mono- or bicyclic. The term“heterocyclylalkyl” refers to an alkyl group substituted by aheterocyclyl, wherein the alkyl and heterocyclyl portions independentlyare optionally substituted.

As used herein, the term “partially unsaturated” refers to a ring moietythat includes at least one double or triple bond. The term “partiallyunsaturated” is intended to encompass rings having multiple sites ofunsaturation, but is not intended to include aryl or heteroarylmoieties, as herein defined.

As described herein, compounds of the invention may contain “optionallysubstituted” moieties. In general, the term “substituted”, whetherpreceded by the term “optionally” or not, means that one or morehydrogens of the designated moiety are replaced with a suitablesubstituent. Unless otherwise indicated, an “optionally substituted”group may have a suitable substituent at each substitutable position ofthe group, and when more than one position in any given structure may besubstituted with more than one substituent selected from a specifiedgroup, the substituent may be either the same or different at everyposition. Combinations of substituents envisioned by this invention arepreferably those that result in the formation of stable or chemicallyfeasible compounds. The term “stable”, as used herein, refers tocompounds that are not substantially altered when subjected toconditions to allow for their production, detection, and, in certainembodiments, their recovery, purification, and use for one or more ofthe purposes disclosed herein.

In some chemical structures herein, substituents are shown attached to abond which crosses a bond in a ring of the depicted molecule. This meansthat one or more of the substituents may be attached to the ring at anyavailable position (usually in place of a hydrogen atom of the parentstructure). In cases where an atom of a ring so substituted has twosubstitutable positions, two groups may be present on the same ringatom. When more than one substituent is present, each is definedindependently of the others, and each may have a different structure. Incases where the substituent shown crossing a bond of the ring is —R,this has the same meaning as if the ring were said to be “optionallysubstituted” as described in the preceding paragraph.

Suitable monovalent substituents on a substitutable carbon atom of an“optionally substituted” group are independently halogen;—(CH₂)₀₋₄R^(∘); —(CH₂)₀₋₄OR^(∘); —O—(CH₂)₀₋₄C(O)OR^(∘);—(CH₂)₀₋₄CH(OR^(∘))₂; —(CH₂)₀₋₄SR^(∘); —(CH₂)₀₋₄Ph, which may besubstituted with R^(∘); —(CH₂)₀₋₄O(CH₂)₀₋₁Ph which may be substitutedwith R^(∘); —CH═CHPh, which may be substituted with R^(∘); —NO₂; —CN;—N₃; —(CH₂)₀₋₄N(R^(∘))₂; —(CH₂)₀₋₄N(R^(∘))C(O)R^(∘); —N(R^(∘)C(S)R^(∘);—(CH₂)₀₋₄N(R^(∘))C(O)NR^(∘) ₂; —N(R^(∘))C(S)NR^(∘) ₂;—(CH₂)₀₋₄N(R^(∘))C(O)OR^(∘); —N(R^(∘))N(R^(∘))C(O)R^(∘);—N(R^(∘))N(R^(∘))C(O)NR^(∘) ₂; —N(R^(∘))N(R^(∘))C(O)OR^(∘);—(CH₂)₀₋₄C(O)R^(∘); —C(S)R^(∘); —(CH₂)₀₋₄C(O)OR^(∘);—(CH₂)₀₋₄C(O)N(R^(∘))₂; —(CH₂)₀₋₄C(O)SR^(∘); —(CH₂)₀₋₄C(O)OSiR^(β) ₃;—(CH₂)₀₋₄OC(O)R^(∘); —OC(O)(CH₂)₀₋₄SR—, SC(S)SR^(∘);—(CH₂)₀₋₄SC(O)R^(∘); —(CH₂)₀₋₄C(O)NR^(∘) ₂; —C(S)NR^(∘) ₂; —C(S)SR^(∘);—SC(S)SR^(∘), —(CH₂)₀₋₄OC(O)NR^(∘) ₂; —C(O)N(OR^(∘))R^(∘);—C(O)C(O)R^(∘); —C(O)CH₂C(O)R^(∘); —C(NOR^(∘))R^(∘); —(CH₂)₀₋₄SSR^(∘);—(CH₂)₀₋₄S(O)₂R^(∘); —(CH₂)₀₋₄S(O)₂OR^(∘); —(CH₂)₀₋₄OS(O)₂R^(∘);—S(O)₂NR^(∘) ₂; —(CH₂)₀₋₄S(O)R^(∘); —N(R^(∘))S(O)₂NR^(∘) ₂;—N(R^(∘))S(O)₂R^(∘); —N(OR^(∘))R^(∘); —C(NH)NR^(∘) ₂; —P(O)₂R^(∘);—P(O)R^(∘) ₂; —OP(O)R^(∘) ₂; —OP(O)(OR^(∘))₂; SiR^(∘) ₃; —(C₁-C₄straight or branched)alkylene)O—N(R^(∘))₂; or —(C₁₋₄ straight orbranched alkylene)C(O)O—)N(R^(∘))₂, wherein each R^(∘) may besubstituted as defined below and is independently hydrogen, C₁₋₈aliphatic, —CH₂Ph, —O(CH₂)₀₋₁Ph, or a 5-6-membered saturated, partiallyunsaturated, or aryl ring having 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, and sulfur, or, notwithstanding the definitionabove, two independent occurrences of R^(∘), taken together with theirintervening atom(s), form a 3-12-membered saturated, partiallyunsaturated, or aryl mono- or polycyclic ring having 0-4 heteroatomsindependently selected from nitrogen, oxygen, and sulfur, which may besubstituted as defined below.

Suitable monovalent substituents on R^(∘) (or the ring formed by takingtwo independent occurrences of R^(∘) together with their interveningatoms), are independently halogen, —(CH₂)₀₋₂R^(●), -(haloR^(●)),—(CH₂)₀₋₂OH^(●), —(CH₂)₀₋₂OR^(●), —(CH₂)₀₋₂CH(OR^(●))₂; —O(haloR^(●)),—CN, —N₃, —(CH₂)₀₋₂C(O)R^(●), —(CH₂)₀₋₂C(O)OH, —(CH₂)₀₋₂C(O)OR^(●),—(CH₂)₀₋₄C(O)N(R^(∘))₂; —(CH₂)₀₋₂SR^(●), —(CH₂)₀₋₂SH, —(CH₂)₀₋₂NH₂,—(CH₂)₀₋₂NHR^(●), —(CH₂)₀₋₂NR^(●) ₂, —NO₂, —SiR^(●) ₃, —OSiR^(●) ₃,—C(O)SR^(●), —(C₁₋₄ straight or branched alkylene)C(O)OR^(●), or—SSR^(●) wherein each R^(●) is unsubstituted or where preceded by “halo”is substituted only with one or more halogens, and is independentlyselected from C₁₋₄ aliphatic, —CH₂Ph, —O(CH₂)₀₋₁Ph, or a 5-6-memberedsaturated, partially unsaturated, or aryl ring having 0-4 heteroatomsindependently selected from nitrogen, oxygen, and sulfur. Suitabledivalent substituents on a saturated carbon atom of R^(∘) include ═O and═S.

Suitable divalent substituents on a saturated carbon atom of an“optionally substituted” group include the following: ═O, ═S, ═NNR*₂,═NNHC(O)R*, ═NNHC(O)OR*, ═NNHS(O)₂R*, ═NR*, ═NOR*, —OC(R*₂))₂₋₃O—, or—S(C(R*₂))₂₋₃S—, wherein each independent occurrence of R* is selectedfrom hydrogen, C₁₋₆ aliphatic which may be substituted as defined below,or an unsubstituted 5-6-membered saturated, partially unsaturated, oraryl ring having 0-4 heteroatoms independently selected from nitrogen,oxygen, and sulfur. Suitable divalent substituents that are bound tovicinal substitutable carbons of an “optionally substituted” groupinclude: —O(CR*₂)₂₋₃O—, wherein each independent occurrence of R* isselected from hydrogen, C₁₋₆ aliphatic which may be substituted asdefined below, or an unsubstituted 5-6-membered saturated, partiallyunsaturated, or aryl ring having 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, and sulfur.

Suitable substituents on the aliphatic group of R* include halogen,—R^(●), -(haloR^(●)), —OH, —OR^(●), —O(haloR^(●)), —CN, —C(O)OH,—C(O)OR^(●), —NH₂, —NHR^(●), —NR^(●) ₂, or —NO₂, wherein each R^(●) isunsubstituted or where preceded by “halo” is substituted only with oneor more halogens, and is independently C₁₋₄ aliphatic, —CH₂Ph,—O(CH₂)₀₋₁Ph, or a 5-6-membered saturated, partially unsaturated, oraryl ring having 0-4 heteroatoms independently selected from nitrogen,oxygen, and sulfur.

Suitable substituents on a substitutable nitrogen of an “optionallysubstituted” group include —R^(†), —NR^(†) ₂, —C(O)R^(†), —C(O)OR^(†),—C(O)C(O)R^(†), —C(O)CH₂C(O)R^(†), —S(O)₂R^(†), —S(O)₂NR^(†) ₂,—(S)NR^(†) ₂, or —N(R^(†))S(O)₂R^(†); wherein each R^(†) isindependently hydrogen, C₁₋₆ aliphatic which may be substituted asdefined below, unsubstituted —OPh, or an unsubstituted 5-6-memberedsaturated, partially unsaturated, or aryl ring having 0-4 heteroatomsindependently selected from nitrogen, oxygen, and sulfur, or,notwithstanding the definition above, two independent occurrences ofR^(†), taken together with their intervening atom(s) form anunsubstituted 3-12-membered saturated, partially unsaturated, or arylmono- or bicyclic ring having 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, and sulfur.

Suitable substituents on the aliphatic group of R^(†) are independentlyhalogen, —R^(●), -(haloR^(●)), —OH, —OR^(●), —O(haloR^(●)), —CN,—C(O)OH, —C(O)OH, —C(O)OR^(●), —NH₂, —NHR^(●), —NR^(●) ₂, or —NO₂,wherein each R^(●) is unsubstituted or where preceded by “halo” issubstituted only with one or more halogens, and is independently C₁₋₄aliphatic, —CH₂Ph, —O(CH₂)₀₋₁Ph, or a 5-6-membered saturated, partiallyunsaturated, or aryl ring having 0-4 heteroatoms independently selectedfrom nitrogen, oxygen, and sulfur.

As used herein, the term “catalyst” refers to a substance the presenceof which increases the rate of a chemical reaction, while not beingconsumed or undergoing a permanent chemical change itself.

“Tetradentate” refers to ligands having four sites capable ofcoordinating to a single metal center.

As used herein, the term “about” preceding one or more numerical valuesmeans the numerical value ±5%.

DETAILED DESCRIPTION OF THE INVENTION Methods of the Invention

In a first aspect, the present invention provides methods for thecontinuous reaction of an epoxide and carbon monoxide. The methodsutilize a carbonylation reactor in which the epoxide and carbon monoxideare contacted in the presence of a carbonylation catalyst to produce areaction product stream. Typically, the reactor is fed with at leastthree input streams: an epoxide feedstream, a carbon monoxide feed, anda catalyst feedstream (though in certain embodiments additional feedsmay be present, or two or more streams may be combined to lessen thetotal number of separate feed streams). The reaction product streamexits the reactor and contains epoxide carbonylation products, thecatalyst, and optionally unreacted feedstock, solvent, reactionbyproducts and the like. In certain embodiments, the epoxidecarbonylation product comprises a beta lactone, a succinic anhydride, ora polyester. In certain embodiments, the epoxide carbonylation productis not a 3-hydroxy propionic acid or a 3-hydroxy propionaldehyde.

In certain embodiments, methods of the present invention include thesteps of:

-   -   a) feeding a continuous carbonylation reactor during a first        interval of time with a catalyst feed stream comprising a        carbonylation catalyst, an epoxide feedstream comprising an        epoxide, and carbon monoxide such that within the reactor the        epoxide and carbon monoxide react under the influence of the        carbonylation catalyst to form a carbonylation reaction product        selected from the group consisting of: a beta lactone, a        succinic anhydride, or a polyhydroxypropionate, such that a        reaction product stream comprising the epoxide carbonylation        product and the carbonylation catalyst, continuously exits the        reactor,    -   b) treating the reaction product stream to separate at least a        portion of the carbonylation catalyst,    -   c) accumulating carbonylation catalyst collected in step (b)        throughout the first interval of time to obtain a spent        carbonylation catalyst batch,    -   d) feeding a continuous carbonylation reactor during a second        interval of time with a catalyst feed stream wherein at least a        portion of the catalyst in the catalyst feed stream comprises        (or is derived at least in part from) the spent carbonylation        catalyst batch accumulated in step (c).

In certain embodiments, the step of treating the reaction product streamto separate a portion of the carbonylation catalyst entails using aseparation mode selected from the group consisting of: precipitation,adsorption, ion exchange, extraction, and any combination of two or moreof these.

In certain embodiments, the step of treating the reaction product streamto separate a portion of the carbonylation catalyst entailsprecipitating the catalyst. Precipitation of the catalyst can beaccomplished by any known means. Suitable means of precipitating thecatalyst will be apparent to the skilled chemist and may include, butare not limited to: adding a solvent to the reaction product stream inwhich the catalyst (or a component thereof) is poorly soluble, coolingthe reaction product stream, adding a material that interacts with thecatalyst (or a component thereof) to form an insoluble adduct, removingsolvent, excess feedstock, or carbon monoxide from the reaction productstream, and combinations of any two or more of these.

In certain embodiments where the step of treating the reaction productstream to separate a portion of the carbonylation catalyst entailsprecipitation, the precipitation step comprises adding a solvent inwhich the catalyst (or a component of the catalyst) is poorly soluble.In certain embodiments, a non-polar solvent such as an aliphatichydrocarbon, an aromatic hydrocarbon, or condensed phase CO₂ is added toprecipitate the catalyst. In certain embodiments, a solvent selectedfrom butane, pentane, hexane, heptane, octane, cyclopentane,cyclohexane, decalin, higher alkanes, and mixtures of two or morealkanes is added to the reaction product stream to precipitate thecatalyst or a catalyst component. In certain embodiments, a solventselected from benzene, toluene, xylene, mesitylene, chlorobenzene, orother substituted benzene compounds is added to the reaction productstream to precipitate the catalyst or a catalyst component. In certainembodiments, supercritical CO₂ is added to the reaction product streamto precipitate the catalyst or a catalyst component. In certainembodiments where the carbonylation catalyst comprises the combinationof a Lewis acidic metal complex and a metal carbonyl compound and anon-polar solvent is added to the reaction product stream, this causesprecipitation of the Lewis acidic metal complex but leaves at least aportion of the metal carbonyl component of the catalyst behind in thereaction product stream.

In embodiments where the catalyst is precipitated, the step ofseparating the carbonylation catalyst typically includes further stepsto remove the precipitate from the product stream, such isolation stepsare well known in the art and can include, but are not limited tofiltration, sedimentation, centrifugation, coagulation, and combinationsof two or more of these.

Therefore, in certain embodiments, the present invention encompassesmethods having the steps of:

-   -   a) feeding a continuous carbonylation reactor during a first        interval of time with a catalyst feed stream comprising a        carbonylation catalyst, an epoxide feed stream comprising an        epoxide, and carbon monoxide such that within the reactor, the        epoxide and carbon monoxide react under the influence of the        carbonylation catalyst to form a carbonylation reaction product        selected from the group consisting of: a beta lactone, a        succinic anhydride, and a polyhydroxypropionate, wherein a        reaction product stream comprising the epoxide carbonylation        product and the carbonylation catalyst exits the reactor,    -   b) adding to the reaction product stream a solvent selected from        the group consisting of: condensed phase CO₂, an alkane, an        aliphatic hydrocarbon, and an aromatic hydrocarbon thereby        causing at least a portion of the carbonylation catalyst to        precipitate from the reaction product stream and separating the        precipitated carbonylation catalyst from the reaction product        stream,    -   c) accumulating carbonylation catalyst collected in step (b)        throughout the first interval of time to obtain a spent        carbonylation catalyst batch,    -   d) feeding a continuous carbonylation reactor during a second        interval of time with a catalyst feed stream wherein at least a        portion of the catalyst in the catalyst feed stream comprises        (or is derived at least in part from) the spent carbonylation        catalyst batch accumulated in step (c).

In certain embodiments, the step of treating the reaction product streamto separate carbonylation catalyst comprises adsorbing the catalyst orcatalyst components. The step of adsorption can entail treating thereaction product stream with a solid adsorbing material. Suitable solidadsorbing materials include inorganic substances, activated carbon,polymers, resins, or any combination of two or more of these. Suitableinorganic adsorbing materials include silica gel, alumina, silicateminerals, clays, diatomaceous earth, Fuller's earth, ceramics,zirconias, molecular sieves and the like. Suitable polymers includepolystyrenes, polyacrylonitrile, polyimides, polyolefins, polyesters,polyethers, polycarbonates, polyisocyanates, and the like. Such polymersoptionally include additional chemical functional groups to enhancetheir ability to adsorb carbonylation catalysts or catalyst components.Such functional groups can include acids (i.e. sulfonic or carboxylicacids), coordinating groups (i.e. amine, thiol, phosphine, nitrile, orboron groups), bases, (for example amine groups or nitrogenheterocycles). In certain cases, the adsorbing materials whetherinorganic or polymeric are acidic, basic, or have undergone chemicaltreatments to enhance the affinity of the catalyst.

In embodiments where catalyst is removed from the reaction productstream by adsorption, the adsorbant can be contacted with the productstream by any conventional method. This includes, but is not limited to:flowing the reaction product stream through a fixed bed of adsorbent;flowing the reaction product stream through a fluidized bed ofadsorbant; flowing the reaction product stream through fabrics, meshes,or filtration plates comprising the adsorbant material; or slurrying thereaction product stream with the adsorbant material (typically followedby filtration, centrifugation, sedimentation or the like to remove theadsorbant from the product stream). In embodiments where the reactionproduct stream is flowed through a column of adsorbant, it may bedesirable to provide a plurality of such columns in parallel with aprovision to switch the flow from one column to another. Thus when onecolumn of adsorbant becomes saturated with catalyst, it can be switchedout of the flow path and the flow diverted to a fresh column—in certainembodiments, the interval of time from when a column is placed in theflow path to when it is switched out of the flow path corresponds to the“first time interval” recited in the methods described herein.

Where an adsorbant is used to remove catalyst from the reaction productstream, the inventive methods will typically include a step of desorbingthe catalyst or catalyst component(s) from the adsorbant. Suchdesorption methods are well known in the art and will vary depending onthe identity of the adsorbant and the catalyst. Desorption can includetreating with a polar solvent or solute which displaces the catalyst orcatalyst component, or can comprise a reactive process where the areagent is added to the adsorbed catalyst to regenerate it or form aspecies which is less adhered to the adsorbing solid.

Therefore, in certain embodiments, the present invention encompassesmethods having the steps of:

-   -   a) feeding the continuous carbonylation reactor during a first        interval of time with a catalyst feed stream comprising a        carbonylation catalyst, an epoxide feedstream comprising an        epoxide, and carbon monoxide such that within the reactor, the        epoxide and carbon monoxide react under the influence of the        carbonylation catalyst to provide a reaction product stream        exiting the reactor and comprising an epoxide carbonylation        product and carbonylation catalyst,    -   b) contacting the reaction product stream with a solid material        which adsorbs at least a portion of the carbonylation catalyst        from the reaction product stream,    -   c) accumulating carbonylation catalyst adsorbed in step (b)        throughout the first interval of time and processing it to        obtain a spent carbonylation catalyst batch,    -   d) feeding a continuous carbonylation reactor during a second        interval of time with a catalyst feed stream wherein at least a        portion of the catalyst in the catalyst feed stream comprises        (or is derived at least in part from) the spent carbonylation        catalyst batch accumulated in step (c).

In certain embodiments, the step of treating the reaction product streamto separate carbonylation catalyst comprises ion exchange of thecatalyst or catalyst components. In certain embodiments, the step oftreating the reaction product stream to separate carbonylation catalystcomprises treating the reaction product stream with ion exchangematerials. The ion exchange materials may be cationic, anionic,amphoteric, Lewis basic, Lewis acidic or may comprise chelating groups.In certain embodiments, the ion exchange material may be a cationexchanger. In certain embodiments, functional groups on the cationexchange materials may be selected from the group: —SO₃

, PO₃ ²⁻, —COOH, —C₆H₄OH, —SH, AsO₃

, —SeO₃

, or combinations of two or more of these. In certain embodiments,functional groups on the cation exchange materials comprise —SO₃.

In certain embodiments, the ion exchange material may be an anionexchanger. In certain embodiments, functional groups on the anionexchange materials may be selected from the group: —N⁺(alkyl)₃,—N⁺(CH₃)₃, —N⁺(CH₃)₂C₂H₄OH, —N⁺(CH₃)₂C₂H₅, —P⁺(alkyl)₃, —P⁺(aryl)₃,—P⁺(C₄H₉)₃, —P⁺(Ph)₃, or combinations of two or more of these. Incertain embodiments, functional groups on the anion exchange materialscomprise —N⁺(alkyl)₃. In certain embodiments, functional groups on theanion exchange materials comprise —P⁺(alkyl)₃. In certain embodiments,functional groups on the anion exchange materials comprise —P⁺(aryl)₃.

In certain embodiments where the step of treating the reaction productstream to separate carbonylation catalyst comprises ion exchange, theprocess entails both anion exchange and cation exchange. In certainembodiments, where the carbonylation catalyst comprises the combinationof a cationic Lewis acid and an anionic metal carbonyl, each is removedseparately and the method comprises treating the reaction product streamwith a cation exchange material to remove the Lewis acid and an anionexchange material to remove the metal carbonyl. In certain embodimentsthe anion and cation exchange are performed concomitantly. In certainembodiments, the anion and cation exchange are performed sequentially.In certain embodiments, the anion exchange is performed first followedby cation exchange. In certain embodiments, the cation exchange isperformed first followed by anion exchange.

In certain embodiments, an ion exchange material used in the separationstep comprises an organic ion exchange resin. Organic ion exchangeresins generally possess a three dimensional structure, a matrix.Functional groups maybe attached to the structure, or directlyincorporated in the polymeric chains. The matrix may be constructed fromlinear polymeric chains cross-linked with each other by relatively shortlinks. By way of example, in various aspects, the present disclosureincludes the use of ion exchange materials comprised of sulphonatedpolystyrene cross-linked with divinylbenzene:

In various aspects, ion exchange materials may take the form of gels, orgel resins, distributed across a bead, or other support substrate. Invarious aspects, ion exchange materials may take the form of macroporousresins which have a heterogeneous structure consisting of two phases, agel region comprised of polymers and macroscopic permanent pores. Invarious embodiments of the present disclosure, the ion exchangematerials comprise macroreticular resins which are additionallymacroporous resins in which the gel regions consist of a plurality beadmicro-grains. Ion exchange materials may comprise a wide variety ofmorphologies and forms, including variations in porosity and othersurface properties. In various aspects, materials can be formed into,but not limited to beads, pellets, spheres, spheroids, rings, hollowcylinders, blocks, fibers, meshes, membranes, textiles. In variousaspects, the bead size may be widely distributed, or may be very narrow,so-called mono-disperse resins.

In embodiments where catalyst is removed from the reaction productstream by ion exchange, the ion exchange material can be contacted withthe product stream by any conventional method. This includes, but is notlimited to: flowing the reaction product stream through a fixed bed of asolid ion exchange material (i.e. in the form of beads, granules orother particles); flowing the reaction product stream through afluidized bed of adsorbant, flowing the reaction product stream throughfabrics, meshes, or filtration plates comprising the ion exchangematerial, or slurrying the reaction product stream with the ion exchangematerial (typically followed by filtration, centrifugation,sedimentation or the like to remove the ion exchange material from theproduct stream). In embodiments where the reaction product stream isflowed through a packed column of ion exchange material, it may bedesirable to provide a plurality of such columns in parallel with aprovision to switch the flow from one to another periodically. Thus whenone column of ion exchange material becomes saturated with catalyst, itcan be switched out of the flow path and the flow diverted to a freshcolumn—in certain embodiments, the interval of time from when a columnis placed in the flow path to when it is switched out of the flow pathcorresponds to the “first time interval” recited in the methodsdescribed herein.

Where an ion exchange material is used to remove catalyst from thereaction product stream, the inventive methods will typically include asubsequent step of removing the catalyst or catalyst component(s) fromthe ion exchange material. Such removal methods are well known in theart and typically involve contacting the ion exchange resin with astrong solution of a salt, the anion or cation of which will displacethe catalyst component from the ion exchange material. The specifics ofthis removal step will obviously vary depending on the identity of theadsorbant and the catalyst, but suitable methods are widely known tothose skilled in the art.

Therefore, in certain embodiments, the present invention encompassesmethods having the steps of:

-   -   a) feeding the continuous carbonylation reactor during a first        interval of time with a catalyst feed stream comprising a        carbonylation catalyst, an epoxide feedstream comprising an        epoxide, and carbon monoxide such that within the reactor, the        epoxide and carbon monoxide react under the influence of the        carbonylation catalyst to provide a reaction product stream        exiting the reactor and comprising an epoxide carbonylation        product and carbonylation catalyst,    -   b) contacting the reaction product stream with a first ion        exchange material which captures at least one component of the        carbonylation catalyst from the reaction product stream,    -   c) accumulating carbonylation catalyst in step (b) throughout        the first interval of time and processing the ion exchange        material(s) to obtain a spent carbonylation catalyst batch, and    -   d) feeding a continuous carbonylation reactor during a second        interval of time with a catalyst feed stream wherein at least a        portion of the catalyst in the catalyst feed stream comprises        (or is derived at least in part from) the spent carbonylation        catalyst batch accumulated in step (c).

In certain embodiments, step (b) of the method includes the further stepof treating the reaction product stream with a second ion exchange resinto remove one or more additional components of the carbonylationcatalyst from the reaction product stream. In such embodiments, one orboth of the ion exchange resins may be processed in step (c) to obtainthe spent catalyst batch or batches.

Therefore, in certain embodiments, the present invention encompassesmethods having the steps of:

-   -   a) feeding the continuous carbonylation reactor during a first        interval of time with a catalyst feed stream comprising a        carbonylation catalyst, an epoxide feedstream comprising an        epoxide, and carbon monoxide such that within the reactor, the        epoxide and carbon monoxide react under the influence of the        carbonylation catalyst to provide a reaction product stream        exiting the reactor and comprising an epoxide carbonylation        product and carbonylation catalyst,    -   b) contacting the reaction product stream with a first ion        exchange material which captures at least one component of the        carbonylation catalyst from the reaction product stream, and        then treating the reaction product stream with a second ion        exchange material that removes one or more additional components        from the reaction product stream, wherein if the first ion        exchange material is an anion exchanger, then the second ion        exchanger is a cation exchanger or vice versa,    -   c) accumulating the removed carbonylation catalyst in step (b)        throughout the first interval of time and processing at least        one of the ion exchange materials to obtain a spent        carbonylation catalyst batch, and    -   d) feeding a continuous carbonylation reactor during a second        interval of time with a catalyst feed stream wherein at least a        portion of the catalyst in the catalyst feed stream comprises        (or is derived at least in part from) the spent carbonylation        catalyst batch accumulated in step (c).

In certain embodiments carbonylation catalyst is removed from thereaction product stream by extraction. In such embodiments, theextraction step comprises adding a solvent in which the catalyst (or acomponent of the catalyst) is soluble. In other embodiments, theextraction solvent is one in which the product is soluble, but which haslittle tendency to dissolve the carbonylation catalyst (or one or morecomponents of the carbonylation catalyst). Preferably, in either case,the addition of the extraction solvent results in the formation of twophases.

In certain embodiments, the extraction solvent is a highly polar solventsuch as water or an ionic liquid. In certain embodiments, the extractionsolvent is supercritical CO₂. In certain embodiments, the extractionsolvent is water or an aqueous solution. In certain embodiments, theextraction solvent is an ionic liquid. In certain embodiments where thesolvent is an ionic liquid, the ionic liquid has a formula [Cat⁺][X″]wherein [Cat⁺] refers to one or more organic cationic species; and [X″]refers to one or more anions. In certain embodiments, [Cat⁺] is selectedfrom the group consisting of: ammonium, tetralkylammonium,benzimidazolium, benzofuranium, benzothiophenium, benzotriazolium,borolium, cinnolinium, diazabicyclodecenium, diazabicyclononenium,1,4-diazabicyclo[2.2.2]octanium, diazabicyclo-undecenium, dithiazolium,furanium, guanidinium, imidazolium, indazolium, indolinium, indolium,morpholinium, oxaborolium, oxaphospholium, oxazinium, oxazolium,iso-oxazolium, oxothiazolium, phospholium, phosphonium, phthalazinium,piperazinium, piperidinium, pyranium, pyrazinium, pyrazolium,pyridazinium, pyridinium, pyrimidinium, pyrrolidinium, pyrrolium,quinazolinium, quinolinium, iso-quinolinium, quinoxalinium,quinuclidinium, selenazolium, sulfonium, tetrazolium, thiadiazolium,iso-thiadiazolium, thiazinium, thiazolium, iso-thiazolium, thiophenium,thiuronium, triazinium, triazolium, iso-triazolium, uronium, and anycombination of two or more of these. In accordance with the presentinvention, [X″] may comprise an anion selected from halides, sulphates,sulfonates, sulfonimides, phosphates, phosphonates, carboxylates, CN⁻,NO₃ ⁻, NO₂ ⁻, BF₄ ⁻ and PF₆ ⁻.

Therefore, in certain embodiments, the present invention encompassesmethods having the steps of:

-   -   a) feeding the continuous carbonylation reactor during a first        interval of time with a catalyst feed stream comprising a        carbonylation catalyst, an epoxide feedstream comprising an        epoxide, and carbon monoxide such that within the reactor, the        epoxide and carbon monoxide react under the influence of the        carbonylation catalyst to provide a reaction product stream        exiting the reactor and comprising an epoxide carbonylation        product and carbonylation catalyst,    -   b) adding to the reaction product stream an extraction solvent        selected from the group consisting of: water, condensed phase        CO₂, and an ionic liquid, thereby causing formation of two        phases wherein the carbonylation catalyst (or at least one        component of the carbonylation catalyst) is at least to some        extent partitioned from the carbonylation reaction product        across the two phases,        -   separating and treating a phase containing carbonylation            catalyst (or a component of the carbonylation catalyst) to            recover the catalyst or catalyst or catalyst component,    -   c) accumulating carbonylation catalyst or component collected in        step (b) throughout the first time interval to obtain a spent        carbonylation catalyst batch,    -   d) feeding a continuous carbonylation reactor during a second        interval of time with a catalyst feed stream wherein at least a        portion of the catalyst in the catalyst feed stream comprises        (or is derived at least in part from) the spent carbonylation        catalyst batch accumulated in step (c).

The Accumulating Step

As noted above, one of the features of methods of the present inventionis accumulation of recovered carbonylation catalyst throughout a timeinterval. In the present methods, the carbonylation catalyst (or acomponent thereof) separated from the reaction product stream isaccumulated through some interval of time. The accumulated catalyst (orcomponent) forms a spent catalyst batch that is eventually reused(either in whole or in part) in a carbonylation process. The process forwhich the catalyst is re-used may or may not be the same process fromwhich the catalyst was isolated. Likewise it may be reused for the sameprocess but on another day or in a different reactor. This is in starkcontrast to prior art methods wherein the separated catalyst is treatedas a stream within the reaction process which is returned to the reactorwithin a relatively short period.

One potential advantage of the present methods is the removal of theconstraint that the catalyst be recovered in active form. For examples,many carbonylation catalysts used in the processes described hereincontain metal carbonyl species which are known to have limited stabilityunder conditions lacking a pressurized atmosphere of CO. Therefore incertain embodiments of the present methods, the carbonlyation catalystis recovered in a form other than as active catalyst. To complete thecatalyst recycle method in such embodiments one or more additional stepsto regenerate the catalyst must be performed.

In certain embodiments, where the carbonylation catalyst comprises acationic Lewis acid in combination with an anionic metal carbonyl, thecationic Lewis acid portion of the catalyst is captured from thecarbonylation stream without the associated metal carbonyl. This isfeasible since the Lewis acid portion of the catalyst is typically themost expensive catalyst component. In certain embodiments, the cationicLewis acid is accumulated in a form with a counterion other than theanionic metal carbonyl. In such embodiments, the methods may include afurther step of treating the accumulated batch of cationic Lewis acidunder conditions to swap a non metal carbonyl anion associated with theaccumulated Lewis acid with a metal carbonyl anion.

In certain embodiments, where the carbonylation catalyst comprises acationic Lewis acid in combination with an anionic metal carbonyl, themetal carbonyl portion of the catalyst is captured from thecarbonylation stream without the associated Lewis acid. The metalcarbonyl thus accumulated may be captured as an anionic metal carbonyl(for example by anion exchange) or it may be accumulated in another formsuch as a reduced metal species, a metal salt, a neutral metal carbonyl,a mixed metal carbonyl complex, or some other form. In such embodiments,the methods may include a further step of treating the accumulatedspecies to regenerate a catalytically active metal carbonyl compound. Inthe case where an intact metal carbonyl anion is accumulated (forexample by capture on an anion exchange resin), such steps may includemetathesis to free the metal carbonyl anion from the resin. This willtypically entail flooding the resin with another anion (such as sodiumchloride) to displace the metal carbonyl. The metal carbonyl may then beobtained as its sodium salt and utilized to produce active catalystaccording to known catalyst synthesis procedures. Therefore, in certainembodiments, methods of the present invention comprise further steps offreeing accumulated metal carbonyl anion from a resin. In certainembodiments, such steps entail further steps of utilizing accumulatedmetal carbonyl anion to regenerate active catalyst by combining theaccumulated metal carbonyl with a suitable Lewis acid.

In certain embodiments, the metal carbonyl may be accumulated in a formother than as an intact metal carbonyl anion. For example, inCO-deficient atmospheres, the metal carbonyl may lose one or more COligands to form multinuclear metal carbonyl species, salts, orprecipitate in elemental form. In other embodiments, a strong ligand mayutilized to displace one or more CO ligands and aid in capture of themetal carbonyl as a new complex. It is well known that such species canbe utilized to regenerate well defined metal carbonyl compounds bytreatment under CO pressure. Therefore, in certain embodiments, methodsof the present invention include further steps of regenerating thecatalytically active metal carbonyl species from a non-catalyticallyactive material accumulated from the reaction product stream. In certainembodiments, such steps entail further steps of treating accumulatedresidue derived from a catalytically active metal carbonyl compoundunder conditions to regenerate a catalytically active metal carbonylsuitable for reuse. In certain embodiments, such steps include a step oftreating the accumulated residue under high CO pressure. In certainembodiments, methods include the step of treating a cobalt-containingresidue accumulated from the reaction product stream under conditions ofhigh CO pressure to convert it to dicobalt octacarbonyl.

In certain embodiments where the accumulation of catalyst separated fromthe reaction product stream comprises steps of recovering two or moreseparate catalyst components in separate recovered catalyst batches,methods of the present invention comprise additional steps ofrecombining recovered catalyst components to produce activecarbonylation catalyst. In some cases the recovered catalyst componentsmay be combined directly while in other steps one or more of thecomponents may require processing as described above prior to the stepof combining. In certain embodiments such steps entail a metathesis torecombine a recovered cationic Lewis acid with a recovered metalcarbonyl anion such as a carbonyl cobaltate.

Another feature of the accumulation step is that it occurs during a timeinterval during which the reactor is being fed and product is beingwithdrawn, meaning that none of the catalyst accumulated is recycledduring the interval. The time interval required to accumulate a batch isdependent on the mode of accumulation, and the scale and economics ofany processes required to transform the accumulated catalyst residueinto active catalyst. Typically the time interval for accumulation ofthe catalyst or residue is on the order of hours to days, but may evenbe weeks. Therefore in certain embodiments of any of the methodsdescribed above, the first time interval is in the range from about 1hour to about 200 hours. In certain embodiments, the first time intervalis from about 2 hours to about 8 hours, from about 4 hours to about 16hours, from about 12 hours to about 24 hours, or from about 16 hours toabout 36 hours. In certain embodiments, the first time interval is fromabout 1 day to about 20 days, from about 1 day to about 3 days, fromabout 2 days to about 5 days, from about 5 days to about 10 days, orfrom about 10 days to about 20 days.

During this time, the carbonylation reactor is fed from a reservoir ofcatalyst which is depleted as the amount of accumulated catalyst (orcatalyst residue) increases on the back end of the process. Additionaltime is then typically required to process the accumulated catalyst orcatalyst residue to remanufacture active catalyst. Therefore somemultiple of the first time interval will have elapsed from the firsttime interval when the catalyst was accumulated to the later time atwhich the carbonylation reactor is fed with a catalyst feed streamcontaining catalyst derived from the catalyst accumulated during thefirst time interval (i.e. step (d)). In certain embodiments the lengthof time between the second time interval (during with catalyst recoveredin step (c) is fed to reactor as recited in step (d) of the methodsabove), and the first time interval (during which the catalyst wasacuumulated) is on the order of about 1 to about 100 times the length ofthe first time interval. In other words if the first time interval is 10hours, the second time interval would occur from about 10 hours to about2000 hours after the completion of the accumulation step. In certainembodiments, the length of time between the second time interval and thefirst time interval is from about 1 to about 10 times the length of thefirst time interval. In certain embodiments, the length of time betweenthe second time interval and the first time interval is from about 1 toabout 3 times, from about 2 to about 5 times, from about 4 to about 10times, from about 10 to about 50 times, from about 40 to about 80 times,or from about 50 to about 100 times, the length of the first timeinterval. In certain embodiments, the length of time between the secondtime interval and the first time interval is greater than 100 times thefirst time interval.

Additional Processing Steps

In certain embodiments, methods encompassed by the present inventioncomprise additional steps to isolate the carbonylation product from thereaction product stream. These steps are generally executed after step(b) of the methods described above and typically entail furthertreatment of the product stream from which the catalyst or catalystcomponent has been substantially removed.

The precise mode of carrying out the carbonylation product isolationwill obviously depend on the character of the carbonylation product.Suitable isolation methods include but are not limited to; distillation,crystallization, precipitation, evaporation, and the like. Inembodiments where the carbonylation product is a liquid such asbetapropiolactone or betabutyrolactone, the methods may comprise anadditional step of performing distillation to separate the lactone fromother components of the reaction product stream. Such other componentscan include solvent(s), unreacted epoxide, reaction byproducts, catalystresidues and the like. In embodiments where the solvent has a lowerboiling point than the lactone, or where unreacted epoxide is present,the beta lactone may be retained as the bottoms in the distillation withthe solvent and/or epoxide taken to the vapor phase. In embodiments,where the solvent has a boiling point higher than the lactone and/orwhere involatile catalyst residues are present, the lactone may be takento the vapor phase. In certain embodiments the catalyst and/or unreactedepoxide are captured and fed back to the epoxide carbonylation reactor(either in real time, or via accumulation and use ata later time).

In embodiments where the carbonylation product is a solid such assuccinic anhydride or polypropiolactone, the methods may comprise anadditional step of performing a crystallization or precipitation toseparate the carbonylation product from other components of the reactionproduct stream. Such other components can include solvent(s), unreactedepoxide, reaction byproducts, catalyst residues and the like. In certainembodiments, such methods include a step of lowering the temperature ofthe reaction product stream. In certain embodiments, such methodsinclude removing solvent, excess epoxide and/or unreacted CO from thereaction product stream. In certain embodiments, such methods compriseadding a solvent to the reaction product stream to cause precipitationor crystallization of the carbonylation product.

In certain embodiments, the methods described above may includeadditional steps intermediate between the carbonylation reactions instep (a) and the catalyst separations in step (b). In certainembodiments, such steps include reduction of the CO pressure. In certainembodiments, the CO pressure is reduced to atmospheric pressure. Incertain embodiments, excess CO is removed by exposure to sub-atmosphericpressures or by sweeping with another gas. In certain embodiments, theCO thus liberated is captured for re-use or is incinerated to provideheat. In certain embodiments, the methods comprise heating or coolingthe reaction product stream between steps (a) and (b). When methodsinclude separation of a solid carbonylation product, they will typicallyinclude additional substeps such as filtration, washing and collectionof the solid product.

Epoxide Feedstock

In certain embodiments, the epoxide in the epoxide feedstream in any ofthe methods described above has a formula:

where,

-   -   R¹ and R² are each independently selected from the group        consisting of: —H; optionally substituted C₁₋₆ aliphatic;        optionally substituted phenyl; optionally substituted C₁₋₆        heteroaliphatic; optionally substituted 3- to 6-membered        carbocycle; and optionally substituted 3- to 6-membered        heterocycle, where R¹ and R² can optionally be taken together        with intervening atoms to form a 3- to 10-membered, substituted        or unsubstituted ring optionally containing one or more        heteroatoms.

In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is phenyl.In some embodiments, R¹ is optionally substituted C₁₋₆ aliphatic. Insome embodiments, R¹ is n-butyl. In some embodiments, R¹ is n-propyl. Insome embodiments, R¹ is ethyl. In some embodiments, R¹ is —CF₃. In someembodiments, R¹ is —CH₂Cl. In other embodiments, R¹ is methyl.

In some embodiments, R² is hydrogen. In some embodiments, R² isoptionally substituted C₁₋₆ aliphatic. In some embodiments, R² ismethyl.

In certain embodiments, R¹ and R² are taken together with interveningatoms to form a 3- to 10-membered, substituted or unsubstituted ringoptionally containing one or more heteroatoms. In some embodiments, R¹and R² are taken together with intervening atoms to form a cyclopentylor cyclohexyl ring.

In certain embodiments, an epoxide is chosen from the group consistingof: ethylene oxide, propylene oxide, 1,2-butylene oxide, 2,3-butyleneoxide, epichlorohydrin, cyclohexene oxide, cyclopentene oxide,3,3,3-Trifluoro-1,2-epoxypropane, styrene oxide, a glycidyl ether, and aglycidyl ester.

In certain embodiments, the epoxide is ethylene oxide.

In certain embodiments, the epoxide is propylene oxide.

In certain embodiments, the carbonylation reaction occurring in thereactor in step (a) conforms to Scheme 2:

-   -   where, each of R¹ and R² is as defined above and described in        classes and subclasses herein.

In certain embodiments, the carbonylation reaction conforms to Scheme 3:

-   -   where, R¹ is selected from the group consisting of —H and C₁₋₆        aliphatic.

In certain embodiments, the carbonylation reaction conforms to Scheme 4where the epoxide is propylene oxide and the carbonylation product isbeta butyrolactone:

In certain embodiments, the carbonylation reaction comprises thereaction shown in Scheme 5 where the epoxide is ethylene oxide and thecarbonylation product is betapropiolactone:

In certain embodiments, the carbonylation reaction occurring in thereactor in step (a) conforms to Scheme 6:

-   -   where, each of R¹ and R² is as defined above and described in        classes and subclasses herein.

In certain embodiments, the carbonylation reaction conforms to Scheme 7:

-   -   where, R¹ is selected from the group consisting of —H and C₁₋₆        aliphatic.

In certain embodiments, the carbonylation reaction conforms to Scheme 8where the epoxide is propylene oxide and the carbonylation product ismethylsuccinic anhydride:

In certain embodiments, the carbonylation reaction comprises thereaction shown in Scheme 9 where the epoxide is ethylene oxide and thecarbonylation product is succinic anhydride:

In certain embodiments, the carbonylation reaction conforms to Scheme 10where the epoxide is propylene oxide and the carbonylation product ispolyhydroxybutyrate:

In certain embodiments, the carbonylation reaction comprises thereaction shown in Scheme 11 where the epoxide is ethylene oxide and thecarbonylation product is polypropiolactone:

The carbon monoxide can be provide to the reactor in step (a) either asa pure stream or as a mixture of carbon monoxide and one or moreadditional gasses. In some embodiments, carbon monoxide is provided in amixture with hydrogen (e.g., Syngas). The ratio of carbon monoxide andhydrogen can be any ratio, including by not limited to about 1:1, 1:2,1:4, 1:10, 10:1, 4:1, 2:1 or a ratio between any two of these values. Insome embodiments, the carbon monoxide is provided in mixture with gasesas an industrial process gas.

Catalyst

Numerous carbonylation catalysts known in the art are suitable for (orcan be adapted to) methods of the present invention. For example, incertain embodiments, the carbonylation methods utilize a metalcarbonyl-Lewis acid catalyst such as those described in U.S. Pat. No.6,852,865. In other embodiments, the carbonylation step is performedwith one or more of the carbonylation catalysts disclosed in U.S. patentapplication Ser. No. 10/820,958; and Ser. No. 10/586,826. In otherembodiments, the carbonylation step is performed with one or more of thecatalysts disclosed in U.S. Pat. Nos. 5,310,948; 7,420,064; and5,359,081. Additional catalysts for the carbonylation of epoxides arediscussed in a review in Chem. Commun., 2007, 657-674. The entirety ofeach of the preceding references is incorporated herein by reference.

In certain embodiments, the carbonylation catalyst includes a metalcarbonyl compound. Typically, a single metal carbonyl compound isprovided, but in certain embodiments, mixtures of two or more metalcarbonyl compounds are provided. (Thus, when a provided metal carbonylcompound “comprises”, e.g., a neutral metal carbonyl compound, it isunderstood that the provided metal carbonyl compound can be a singleneutral metal carbonyl compound, or a neutral metal carbonyl compound incombination with one or more metal carbonyl compounds.) Preferably, theprovided metal carbonyl compound is capable of ring-opening an epoxideand facilitating the insertion of CO into the resulting metal carbonbond. Metal carbonyl compounds with this reactivity are well known inthe art and are used for laboratory experimentation as well as inindustrial processes such as hydroformylation.

In certain embodiments, a provided metal carbonyl compound comprises ananionic metal carbonyl moiety. In other embodiments, a provided metalcarbonyl compound comprises a neutral metal carbonyl compound. Incertain embodiments, a provided metal carbonyl compound comprises ametal carbonyl hydride or a hydrido metal carbonyl compound. In someembodiments, a provided metal carbonyl compound acts as a pre-catalystwhich reacts in situ with one or more reaction components to provide anactive species different from the compound initially provided. Suchpre-catalysts are specifically encompassed by the present invention asit is recognized that the active species in a given reaction may not beknown with certainty; thus the identification of such a reactive speciesin situ does not itself depart from the spirit or teachings of thepresent invention.

In certain embodiments, the metal carbonyl compound comprises an anionicmetal carbonyl species. In certain embodiments, such anionic metalcarbonyl species have the general formula [Q_(d)M′_(e)(CO)_(w)]^(y−),where Q is any ligand and need not be present, M′ is a metal atom, d isan integer between 0 and 8 inclusive, e is an integer between 1 and 6inclusive, w is a number such as to provide the stable anionic metalcarbonyl complex, and y is the charge of the anionic metal carbonylspecies. In certain embodiments, the anionic metal carbonyl has thegeneral formula [QM′(CO)_(w)]^(y−), where Q is any ligand and need notbe present, M′ is a metal atom, w is a number such as to provide thestable anionic metal carbonyl, and y is the charge of the anionic metalcarbonyl.

In certain embodiments, the anionic metal carbonyl species includemonoanionic carbonyl complexes of metals from groups 5, 7 or 9 of theperiodic table or dianionic carbonyl complexes of metals from groups 4or 8 of the periodic table. In some embodiments, the anionic metalcarbonyl compound contains cobalt or manganese. In some embodiments, theanionic metal carbonyl compound contains rhodium. Suitable anionic metalcarbonyl compounds include, but are not limited to: [Co(CO)₄]⁻,[Ti(CO)₆]²⁻[V(CO)₆]⁻[Rh(CO)₄]⁻, [Fe(CO)₄]²⁻[Ru(CO)₄]²⁻,[Os(CO)₄]²⁻[Cr₂(CO)₁₀]²⁻[Fe₂(CO)₈]²⁻[Tc(CO)₅]⁻[Re(CO)₅]⁻ and [Mn(CO)₅]⁻.In certain embodiments, the anionic metal carbonyl comprises [Co(CO)₄]⁻.In some embodiments, a mixture of two or more anionic metal carbonylcomplexes may be present in the carbonylation catalysts used in themethods.

The term “such as to provide a stable anionic metal carbonyl” for[Q_(d)M′_(e)(CO)_(w)]^(y−)″ is used herein to mean that[Q_(d)M′_(e)(CO)_(w)]^(y−) is a species characterizable by analyticalmeans, e.g., NMR, IR, X-ray crystallography, Raman spectroscopy and/orelectron spin resonance (EPR) and isolable in catalyst form in thepresence of a suitable cation or a species formed in situ. It is to beunderstood that metals which can form stable metal carbonyl complexeshave known coordinative capacities and propensities to form polynuclearcomplexes which, together with the number and character of optionalligands Q that may be present and the charge on the complex willdetermine the number of sites available for CO to coordinate andtherefore the value of w. Typically, such compounds conform to the“18-electron rule”. Such knowledge is within the grasp of one havingordinary skill in the arts pertaining to the synthesis andcharacterization of metal carbonyl compounds.

In embodiments where the provided metal carbonyl compound is an anionicspecies, one or more cations must also necessarily be present. Thepresent invention places no particular constraints on the identity ofsuch cations. In certain embodiments, the cation associated with ananionic metal carbonyl compound comprises a reaction component ofanother category described hereinbelow. For example, in certainembodiments, the metal carbonyl anion is associated with a cationicLewis acid. In other embodiments a cation associated with a providedanionic metal carbonyl compound is a simple metal cation such as thosefrom Groups 1 or 2 of the periodic table (e.g. Na⁺, Li⁺, K⁺, Mg²⁺ andthe like). In other embodiments a cation associated with a providedanionic metal carbonyl compound is a bulky non electrophilic cation suchas an ‘onium salt’ (e.g. Bu₄N⁺, PPN⁺, Ph₄P⁺ Ph₄As⁺, and the like). Inother embodiments, a metal carbonyl anion is associated with aprotonated nitrogen compound (e.g. a cation may comprise a compound suchas MeTBD-H⁺, DMAP-H⁺, DABCO-H⁺, DBU-H⁺ and the like). In certainembodiments, compounds comprising such protonated nitrogen compounds areprovided as the reaction product between an acidic hydrido metalcarbonyl compound and a basic nitrogen-containing compound (e.g. amixture of DBU and HCo(CO)₄).

In certain embodiments, a catalyst utilized in the methods describedabove comprises a neutral metal carbonyl compound. In certainembodiments, such neutral metal carbonyl compounds have the generalformula Q_(d)M′_(e)(CO)_(w′), where Q is any ligand and need not bepresent, M′ is a metal atom, d is an integer between 0 and 8 inclusive,e is an integer between 1 and 6 inclusive, and w′ is a number such as toprovide the stable neutral metal carbonyl complex. In certainembodiments, the neutral metal carbonyl has the general formulaQM′(CO)_(w′). In certain embodiments, the neutral metal carbonyl has thegeneral formula M′(CO)_(w′). In certain embodiments, the neutral metalcarbonyl has the general formula QM′₂(CO)_(w′). In certain embodiments,the neutral metal carbonyl has the general formula M′₂(CO)_(w′).Suitable neutral metal carbonyl compounds include, but are not limitedto: Ti(CO)₇; V₂(CO)₁₂; Cr(CO)₆; Mo(CO)₆; W(CO)₆Mn₂(CO)₁₀, Tc₂(CO)₁₀, andRe₂(CO)₁₀Fe(CO)₅, Ru(CO)₅ and Os(CO)₅Ru₃(CO)₁₂, and Os₃(CO)₁₂Fe₃(CO)₁₂and Fe₂(CO)₉Co₄(CO)₁₂, Rh₄(CO)₁₂, Rh₆(CO)₁₆, andIr₄(CO)₁₂Co₂(CO)₈Ni(CO)₄.

The term “such as to provide a stable neutral metal carbonyl forQ_(d)M′_(e)(CO)_(w′) is used herein to mean that Q_(d)M′_(e)(CO)_(w′) isa species characterizable by analytical means, e.g., NMR, IR, X-raycrystallography, Raman spectroscopy and/or electron spin resonance (EPR)and isolable in pure form or a species formed in situ. It is to beunderstood that metals which can form stable metal carbonyl complexeshave known coordinative capacities and propensities to form polynuclearcomplexes which, together with the number and character of optionalligands Q that may be present will determine the number of sitesavailable for CO to coordinate and therefore the value of w′. Typically,such compounds conform to stoichiometries conforming to the “18-electronrule”. Such knowledge is within the grasp of one having ordinary skillin the arts pertaining to the synthesis and characterization of metalcarbonyl compounds.

In certain embodiments, no ligands Q are present on the metal carbonylcompound. In other embodiments, one or more ligands Q are present on themetal carbonyl compound. In certain embodiments, where Q is present,each occurrence of Q is selected from the group consisting of phosphineligands, amine ligands, cyclopentadienyl ligands, heterocyclic ligands,nitriles, phenols, and combinations of two or more of these. In certainembodiments, one or more of the CO ligands of any of the metal carbonylcompounds described above is replaced with a ligand Q. In certainembodiments, Q is a phosphine ligand. In certain embodiments, Q is atriaryl phosphine. In certain embodiments, Q is trialkyl phosphine. Incertain embodiments, Q is a phosphite ligand. In certain embodiments, Qis an optionally substituted cyclopentadienyl ligand. In certainembodiments, Q is cp. In certain embodiments, Q is cp*. In certainembodiments, Q is an amine or a heterocycle.

In certain embodiments, the carbonylation catalyst utilized in themethods described above further includes a Lewis acidic component. Insome embodiments, the carbonylation catalyst includes an anionic metalcarbonyl complex and a cationic Lewis acidic component. In certainembodiments, the metal carbonyl complex includes a carbonyl cobaltateand the Lewis acidic co-catalyst includes a metal-centered cationicLewis acid. In certain embodiments, an included Lewis acid comprises aboron compound.

In certain embodiments, where an included Lewis acid comprises a boroncompound, the boron compound comprises a trialkyl boron compound or atriaryl boron compound. In certain embodiments, an included boroncompound comprises one or more boron-halogen bonds. In certainembodiments, where an included boron compound comprises one or moreboron-halogen bonds, the compound is a dialkyl halo boron compound (e.g.R₂BX), a dihalo monoalkly compound (e.g. RBX₂), an aryl halo boroncompound (e.g. Ar₂BX or ArBX₂), or a trihalo boron compound (e.g. BCl₃or BBr₃).

In certain embodiments, where the included Lewis acid comprises ametal-centered cationic Lewis acid, the Lewis acid is a cationic metalcomplex. In certain embodiments, the cationic metal complex has itscharge balanced either in part, or wholly by one or more anionic metalcarbonyl moieties. Suitable anionic metal carbonyl compounds includethose described above. In certain embodiments, there are 1 to 17 suchanionic metal carbonyls balancing the charge of the metal complex. Incertain embodiments, there are 1 to 9 such anionic metal carbonylsbalancing the charge of the metal complex. In certain embodiments, thereare 1 to 5 such anionic metal carbonyls balancing the charge of themetal complex. In certain embodiments, there are 1 to 3 such anionicmetal carbonyls balancing the charge of the metal complex.

In certain embodiments, where carbonylation catalysts used in methods ofthe present invention include a cationic metal complex, the metalcomplex has the formula [(L^(c))_(v)M_(b)]^(z+), where:

-   -   L^(c) is a ligand where, when two or more L^(c) are present,        each may be the same or different;    -   M is a metal atom where, when two M are present, each may be the        same or different;    -   v is an integer from 1 to 4 inclusive;    -   b is an integer from 1 to 2 inclusive; and    -   z is an integer greater than 0 that represents the cationic        charge on the metal complex.

In certain embodiments, provided Lewis acids conform to structure I:

wherein:

-   -   is a multidentate ligand;    -   M is a metal atom coordinated to the multidentate ligand;    -   a is the charge of the metal atom and ranges from 0 to 2; and

In certain embodiments, provided metal complexes conform to structureII:

-   -   Where a is as defined above (each a may be the same or        different), and    -   M¹ is a first metal atom;    -   M² is a second metal atom;

-   -   comprises a multidentate ligand system capable of coordinating        both metal atoms.

For sake of clarity, and to avoid confusion between the net and totalcharge of the metal atoms in complexes I and II and other structuresherein, the charge (a⁺) shown on the metal atom in complexes I and IIabove represents the net charge on the metal atom after it has satisfiedany anionic sites of the multidentate ligand. For example, if a metalatom in a complex of formula I were Cr(III), and the ligand wereporphyrin (a tetradentate ligand with a charge of −2), then the chromiumatom would have a net chage of +1, and a would be 1.

Suitable multidentate ligands include, but are not limited to: porphyrinderivatives 1, salen derivatives 2,dibenzotetramethyltetraaza[14]annulene (tmtaa) derivatives 3,phthalocyaninate derivatives 4, derivatives of the Trost ligand 5,tetraphenylporphyrin derivatives 6, and corrole derivatives 7. Incertain embodiments, the multidentate ligand is a salen derivative. Inother embodiments, the multidentate ligand is a porphyrin derivative. Inother embodiments, the multidentate ligand is a tetraphenylporphyrinderivative. In other embodiments, the multidentate ligand is a corrolederivative.

-   -   where each of R^(c), R^(d), R^(a), R^(1a), R^(2a), R^(3a),        R^(1a′), R^(2a′), R^(3a′), and M, is as defined and described in        the classes and subclasses herein.

In certain embodiments, Lewis acids provided carbonylation catalystsused in methods of the present invention comprise metal-porphinatocomplexes. In certain embodiments, the moiety

has the structure:

-   -   where each of M and a is as defined above and described in the        classes and subclasses herein, and    -   R^(d) at each occurrence is independently hydrogen, halogen,        —OR⁴, —NR^(y) ₂, —SR, —CN, —NO₂, —SO₂R^(y), —SOR^(y), —SO₂NR^(y)        ₂; —CNO, —NRSO₂R^(y), —NCO, —N₃, —SiR₃; or a optionally        substituted group selected from the group consisting of C₁₋₂₀        aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur; 6- to 10-membered aryl; 5- to 10-membered        heteroaryl having 1-4 heteroatoms independently selected from        nitrogen, oxygen, and sulfur; and 4- to 7-membered heterocyclic        having 1-2 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur, where two or more        R^(d) groups may be taken together to form one or more        optionally substituted rings, where each R^(y) is independently        hydrogen, an optionally substituted group selected the group        consisting of acyl; carbamoyl, arylalkyl; 6- to 10-membered        aryl; C₁₋₁₂ aliphatic; C₁₋₁₂ heteroaliphatic having 1-2        heteroatoms independently selected from the group consisting of        nitrogen, oxygen, and sulfur; 5- to 10-membered heteroaryl        having 1-4 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur; 4- to 7-membered        heterocyclic having 1-2 heteroatoms independently selected from        the group consisting of nitrogen, oxygen, and sulfur; an oxygen        protecting group; and a nitrogen protecting group; two R^(y) on        the same nitrogen atom are taken with the nitrogen atom to form        an optionally substituted 4- to 7-membered heterocyclic ring        having 0-2 additional heteroatoms independently selected from        the group consisting of nitrogen, oxygen, and sulfur; and each        R⁴ independently is a hydroxyl protecting group or R^(y).

In certain embodiments, the moiety

has the structure:

-   -   where M, a and R^(d) are as defined above and in the classes and        subclasses herein.

In certain embodiments, the moiety

has the structure:

-   -   where M, a and R^(d) are as defined above and in the classes and        subclasses herein.

In certain embodiments, Lewis acids included in carbonylation catalystsused in methods of the present invention comprise metallo salenatecomplexes. In certain embodiments, the moiety

has the structure:

wherein:

-   -   M, and a are as defined above and in the classes and subclasses        herein.    -   R^(1a), R^(1a′), R^(2a), R^(2a′), R^(3a), and R^(3a′) are        independently hydrogen, halogen, —OR⁴, —NR^(y) ₂, —SR, —CN,        —NO₂, —SO₂R^(y), —SOR, —SO₂NR^(y) ₂; —CNO, —NRSO₂R^(y), —NCO,        —N₃, —SiR₃; or an optionally substituted group selected from the        group consisting of C₁₋₂₀ aliphatic; C₁₋₂₀ heteroaliphatic        having 1-4 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur; 6- to 10-membered        aryl; 5- to 10-membered heteroaryl having 1-4 heteroatoms        independently selected from nitrogen, oxygen, and sulfur; and 4-        to 7-membered heterocyclic having 1-2 heteroatoms independently        selected from the group consisting of nitrogen, oxygen, and        sulfur; wherein each R, R⁴, and R^(y) is independently as        defined above and described in classes and subclasses herein,    -   wherein any of (R^(2a′) and R^(3a′)), (R^(2a) and R^(3a)),        (R^(1a) and R^(2a)), and (R^(1a′) and R^(2a′)) may optionally be        taken together with the carbon atoms to which they are attached        to form one or more rings which may in turn be substituted with        one or more R groups; and    -   R^(4a) is selected from the group consisting of:

where

-   -   R^(c) at eah occurrence is independently hydrogen, halogen, —OR,        —NR^(y) ₂, —SR^(y), —CN, —NO₂, —SO₂R^(y), —SOR^(y), —SO₂NR^(y)        ₂; —CNO, —NRSO₂R^(y), —NCO, —N₃, —SiR₃; or an optionally        substituted group selected from the group consisting of C₁₋₂₀        aliphatic; C₁₋₂₀ heteroaliphatic having 1-4 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur; 6- to 10-membered aryl; 5- to 10-membered        heteroaryl having 1-4 heteroatoms independently selected from        nitrogen, oxygen, and sulfur; and 4- to 7-membered heterocyclic        having 1-2 heteroatoms independently selected from the group        consisting of nitrogen, oxygen, and sulfur;        where:    -   two or more R^(c) groups may be taken together with the carbon        atoms to which they are attached and any intervening atoms to        form one or more rings;    -   when two R^(c) groups are attached to the same carbon atom, they        may be taken together along with the carbon atom to which they        are attached to form a moiety selected from the group consisting        of: a 3- to 8-membered spirocyclic ring, a carbonyl, an oxime, a        hydrazone, an imine; and an optionally substituted alkene;    -   Y is a divalent linker selected from the group consisting of:        —NR^(y)—, —N(R)C(O)—, —C(O)NR^(y)—, —O—, —C(O(—, —OC(O)—,        —C(O)O—, —S—, —SO—, —SO₂—, —C(═S)—, —C(═NR^(y))—, —N═N—; a C₃ to        C₈ substituted or unsubstituted carbocycle; and a C₁ to C₈        substituted or unsubstituted heterocycle;    -   m′ is 0 or an integer from 1 to 4, inclusive;    -   q is 0 or an integer from 1 to 4, inclusive; and    -   x is 0, 1, or 2.

In certain embodiments, a provided Lewis acid comprises a metallo salencompound, as shown in formula Ia:

-   -   wherein each of M, R^(d), and a, is as defined above and in the        classes and subclasses herein,

-   -   represents is an optionally substituted moiety linking the two        nitrogen atoms of the diamine portion of the salen ligand, where

is selected from the group consisting of a C₃-C₁₄ carbocycle, a C₆-C₁₀aryl group, a C₃-C₁₄ heterocycle, and a C₅-C₁₀ heteroaryl group; or anoptionally substituted C₂₋₂₀ aliphatic group, wherein one or moremethylene units are optionally and independently replaced by —NR^(y)—,—N(R^(y))C(O)—, —C(O)N(R^(y))—, —OC(O)N(R^(y))—, —N(R^(y))C(O)O—,—OC(O)O—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —O—, —SO₂—, —C(═S)—,—C(═NR^(y))—, —C(═NOR^(y))— or —N═N—.

In certain embodiments metal complexes having formula Ia above, at leastone of the phenyl rings comprising the salicylaldehyde-derived portionof the metal complex is independently selected from the group consistingof:

In certain embodiments, a provided Lewis acid comprises a metallo salencompound, conforming to one of formulae Va or Vb:

-   -   where M, a, R^(d), R^(1a), R^(3a), R^(1a′), R^(3a′), and

are as defined above and in the classes and subclasses herein.

In certain embodiments of metal complexes having formulae Va or Vb, eachR^(1′) and R^(3′) is, independently, optionally substituted C₁-C₂₀aliphatic.

In certain embodiments, the moiety

comprises an optionally substituted 1,2-phenyl moiety.

In certain embodiments, Lewis acids included in carbonylation catalystsused in methods of the present invention comprise metal-tmtaa complexes.In certain embodiments, the moiety

has the structure:

-   -   where M, a and R^(d) are as defined above and in the classes and        subclasses herein, and    -   R^(e) at each occurrence is independently hydrogen, halogen,        —OR, —NR₂, —SR, —CN, —NO₂, —SO₂R, —SOR, —SO₂NR₂; —CNO, —NRSO₂R,        —NCO, —N₃, —SiR₃; or an optionally substituted group selected        from the group consisting of C₁₋₂₀ aliphatic; C₁₋₂₀        heteroaliphatic having 1-4 heteroatoms independently selected        from the group consisting of nitrogen, oxygen, and sulfur; 6- to        10-membered aryl; 5- to 10-membered heteroaryl having 1-4        heteroatoms independently selected from nitrogen, oxygen, and        sulfur; and 4- to 7-membered heterocyclic having 1-2 heteroatoms        independently selected from the group consisting of nitrogen,        oxygen, and sulfur.

In certain embodiments, the moiety

has the structure:

-   -   where each of M, a, R^(c) and R^(d) is as defined above and in        the classes and subclasses herein.

In certain embodiments, where carbonylation catalysts used in methods ofthe present invention include a Lewis acidic metal complex, the metalatom is selected from the periodic table groups 2-13, inclusive. Incertain embodiments, M is a transition metal selected from the periodictable groups 4, 6, 11, 12 and 13. In certain embodiments, M is aluminum,chromium, titanium, indium, gallium, zinc cobalt, or copper. In certainembodiments, M is aluminum. In other embodiments, M is chromium.

In certain embodiments, M has an oxidation state of +2. In certainembodiments, M is Zn(II), Cu(II), Mn(II), Co(II), Ru(II), Fe(II),Co(II), Rh(II), Ni(II), Pd(II) or Mg(II). In certain embodiments M isZn(II). In certain embodiments M is Cu(II).

In certain embodiments, M has an oxidation state of +3. In certainembodiments, M is Al(III), Cr(III), Fe(III), Co(III), Ti(III) In(III),Ga(III) or Mn(III). In certain embodiments M is Al(III). In certainembodiments M is Cr(III).

In certain embodiments, M has an oxidation state of +4. In certainembodiments, M is Ti(IV) or Cr(IV).

In certain embodiments, M¹ and M² are each independently a metal atomselected from the periodic table groups 2-13, inclusive. In certainembodiments, M is a transition metal selected from the periodic tablegroups 4, 6, 11, 12 and 13. In certain embodiments, M is aluminum,chromium, titanium, indium, gallium, zinc cobalt, or copper. In certainembodiments, M is aluminum. In other embodiments, M is chromium. Incertain embodiments, M¹ and M² are the same. In certain embodiments, M¹and M² are the same metal, but have different oxidation states. Incertain embodiments, M¹ and M² are different metals.

In certain embodiments, one or more of M¹ and M² has an oxidation stateof +2. In certain embodiments, M¹ is Zn(II), Cu(II), Mn(II), Co(II),Ru(II), Fe(II), Co(II), Rh(II), Ni(II), Pd(II) or Mg(II). In certainembodiments M¹ is Zn(II). In certain embodiments M¹ is Cu(II). Incertain embodiments, M² is Zn(II), Cu(II), Mn(II), Co(II), Ru(II),Fe(II), Co(II), Rh(II), Ni(II), Pd(II) or Mg(II). In certain embodimentsM² is Zn(II). In certain embodiments M² is Cu(II).

In certain embodiments, one or more of M¹ and M² has an oxidation stateof +3. In certain embodiments, M¹ is Al(III), Cr(III), Fe(III), Co(III),Ti(III) In(III), Ga(III) or Mn(III). In certain embodiments M¹ isAl(III). In certain embodiments M¹ is Cr(III). In certain embodiments,M² is Al(III), Cr(III), Fe(III), Co(III), Ti(III) In(III), Ga(III) orMn(III). In certain embodiments M² is Al(III). In certain embodiments M²is Cr(III).

In certain embodiments, one or more of M¹ and M² has an oxidation stateof +4. certain embodiments, M¹ is Ti(IV) or Cr(IV). In certainembodiments, M² is Ti(IV) or Cr(IV).

In certain embodiments, the metal-centered Lewis-acidic component of thecarbonylation catalyst includes a dianionic tetradentate ligand. Incertain embodiments, the dianionic tetradentate ligand is selected fromthe group consisting of: porphyrin derivatives; salen derivatives;dibenzotetramethyltetraaza[14]annulene (tmtaa) derivatives;phthalocyaninate derivatives; and derivatives of the Trost ligand.

In certain embodiments, the carbonylation catalyst includes a carbonylcobaltate in combination with an aluminum porphyrin compound.

In certain embodiments, the carbonylation catalyst includes a carbonylcobaltate in combination with a chromium porphyrin compound.

In certain embodiments, the carbonylation catalyst includes a carbonylcobaltate in combination with a chromium salen compound. In certainembodiments, the carbonylation catalyst includes a carbonyl cobaltate incombination with a chromium salophen compound.

In certain embodiments, the carbonylation catalyst includes a carbonylcobaltate in combination with an aluminum salen compound. In certainembodiments, the carbonylation catalyst includes a carbonyl cobaltate incombination with an aluminum salophen compound.

In certain embodiments, one or more neutral two electron donorscoordinate to M M¹ or M² and fill the coordination valence of the metalatom. In certain embodiments, the neutral two electron donor is asolvent molecule. In certain embodiments, the neutral two electron donoris an ether. In certain embodiments, the neutral two electron donor istetrahydrofuran, diethyl ether, acetonitrile, carbon disulfide, orpyridine. In certain embodiments, the neutral two electron donor istetrahydrofuran . In certain embodiments, the neutral two electron donoris an epoxide. In certain embodiments, the neutral two electron donor isan ester or a lactone.

Solvents

In some embodiments, the carbonylation methods herein are performed in asolvent. In certain embodiments, the solvent is fed to the continuouscarbonylation reactor in step (a) as a separate stream. In otherembodiments, the solvent may be fed to the ractor along with thecatalyst the epoxide or another feedstream entering the carbonylationreactor. In certain embodiments, the solvent enters the carbonylationreactor along with the carbonylation catalyst which is provided as acatalyst solution in the solvent. In certain embodiments, the solvententers the carbonylation reactor in two or more separate feedstreams. Inembodiments where solvent is present in the carbonylation reactor, it isalso present in the carbonylation product stream.

The solvent may be selected from any solvent, and mixtures of solvents.Additionally, beta-lactone may be utilized as a co-solvent. Solventsmost suitable for the methods include ethers, hydrocarbons and nonprotic polar solvents. Examples of suitable solvents include, but arenot limited to: tetrahydrofuran (“THF”), sulfolane, N-methylpyrrolidone, 1,3 dimethyl-2-imidazolidinone, diglyme, triglyme,tetraglyme, diethylene glycol dibutyl ether, isosorbide ethers, methyltertbutyl ether, diethylether, diphenyl ether, 1,4-dioxane, ethylenecarbonate, propylene carbonate, butylene carbonate, dibasic esters,diethyl ether, acetonitrile, ethyl acetate, dimethoxy ethane, acetone,and methylethyl ketone.

In some embodiments, the carbonylation methods further include a Lewisbase additive in the carbonylation reactor. In certain embodiments suchLewis base additives can stabilize or reduce deactivation of thecatalysts. In some embodiments, the Lewis base additive is selected fromthe group consisting of phosphines, amines, guanidines, amidines, andnitrogen-containing heterocycles. In some embodiments, the Lewis baseadditive is a hindered amine base. In some embodiments, the Lewis baseadditive is a 2,6-lutidine; imidazole, 1-methylimidazole,4-dimethylaminopyridine, trihexylamine and triphenylphosphine.

Carbonylation Reaction Conditions

The carbonylation reaction conditions in step (a) of the methods aboveare preferably selected to effect efficient conversion of the epoxide tothe desired product(s). Temperature, pressure, mixing, and reaction timeinfluence reaction speed and efficiency. Additionally the ratio ofreactants to each other and to the catalyst effect reaction speed andefficiency. The control and optimization of these parameters is aroutine matter in the field of chemical engineering and the presentinvention places no particular constraints or limitations on thecarbonylation reaction conditions.

In some embodiments, the reaction temperature can range from betweenabout −20° C., to about 600° C. In some embodiments, the reactiontemperature is about −20° C., about 0° C., about 20° C., about 40° C.,about 60° C., about 80° C., about 100° C., about 200° C., about 300° C.,about 400° C., about 500° C. or about , about 600° C. In someembodiments, the temperature is in a range between about 40° C. andabout 120° C. In some embodiments, the temperature is in a range betweenabout 60° C. and about 140° C. In some embodiments, the temperature isin a range between about 40° C. and about 80° C. In some embodiments,the temperature is in a range between about 50° C. and about 70° C. Insome embodiments, the reactants, catalyst and solvent are supplied tothe reactor at standard temperature, and then heated in the reactor. Insome embodiments, the reactants are pre-heated before entering thereactor.

In some embodiments, the reaction pressure can range from between about50 psig to about 5000 psig. In some embodiments, the reaction pressureis about 100 psig, about 200 psig, about 300 psig, about 400 psig, about500 psig, about 600 psig, about 700 psig, about 800 psig, about 900psig, or about 1000 psig. In some embodiments, the pressure ranges fromabout 50 psig to about 2000 psig. In some embodiments, the pressureranges from about 100 psig to 1000 psig. In some embodiments, thepressure ranges from about 200 psig to about 800 psig. In someembodiments, the pressure ranges from about 800 psig to about 1600 psig.In some embodiments, the pressure ranges from about 1500 psig to about3500 psig. In some embodiments, the pressure ranges from about 3000 psigto about 5500 psig. In some embodiments, the reaction pressure issupplied entirely by the carbon monoxide. For example, carbon monoxideis added to the at reactor at high pressure to increase pressure to thereaction pressure. In some embodiments, all reactants, solvent andcatalyst are supplied to the reactor at reaction pressure.

In some embodiments, the ratio of catalyst to epoxide is selected, basedon other reaction conditions, so that the reaction proceeds in aneconomical and time-feasible manner. In some embodiments, the ratio ofcatalyst to epoxide is about 1:10000 on a molar basis. In someembodiments, the molar ratio of catalyst to epoxide is about 1:5000, isabout 1:2500, is about 1:2000, is about 1:1500, is about 1:1000, isabout 1:750, is about 1:500, is about 1:250, is about 1:200, is about1:150, or is about 1:100. In some embodiments, the concentration of theepoxide is in the range between about 0.1 M and about 5.0 M. In someembodiments, the concentration of the epoxide is in the range betweenabout 0.5 M and about 3.0 M.

In some embodiments, the reaction is maintained for a period of timesufficient to allow complete, near complete reaction of the epoxide tocarbonylation products or as complete as possible based on the reactionkinetics and or reaction conditions. In some mbodiments, the reactiontime is a residence time in the carbonylation reactor in step (a). Incertain embodiments, the residence time is about 12 hours, about 8hours, about 6 hours, about 3 hours, about 2 hours or about 1 hour. Incertain embodiments, the residence time is about 30 minutes, about 20minutes, about 15 minutes, about 10 minutes, about 5 minutes, about 3minutes, about 2 minutes, or about 1 minute. In certain embodiments, theresidence time is less than 1 minute.

Carbonylation Reaction Products

The reaction product stream formed in step (a) of the methods herein maycontain reaction by-products, un-reacted reactants, as well as catalystand the desired carbonylation product. In some embodiments, theun-reacted reactants include epoxide or carbon monoxide. As such, thereaction may not proceed to completion and may be considered a partialreaction.

In some embodiments, where the product of the carbonylation is a betalactone, an amount of un-reacted epoxide is maintained sufficient toprevent the formation of a succinic anhydride by further carbonylationof the beta lactone. Without being bound by a particular theory, it isspeculated that the second reaction converting the beta-lactone tosuccinic anhydride does not proceed unless substantially all of theepoxide is consumed. Thus a remaining portion of the epoxide feed to thereactor that exits un-reacted appears to prevent the formation ofsuccinic anhydride. Therefore, in some embodiments, the reaction productstream contains unconverted epoxide in an amount of at least about 5%epoxide, at least 3% epoxide, at least about 1% epoxide or at leastabout 0.1%, by weight.

Reaction Mode

The methods herein place no particular limits on the type, size orgeometry of the reactor employed and indeed, in some cases, more thanone reactor may be employed. It is to be understood that the term“reactor” as recited in the methods herein may actually represent morethan one physical reactor (for example the reactor could be a train ofcontinuous stirred tank reactors (CSTRs) connected in parallel or inseries, or a plurality of plug flow reactors). In certain embodiments,the “reactor” referred to in the methods herein may also comprise morethan one type of reactor (for example the reactor could comprise a CSTRin series with a plug flow reactor). Many such combinations are known inthe art and could be employed by the skilled artisan to achieve anefficient reaction in step (a) of the methods described herein.

EXAMPLES

In a first example of a process according to the present invention, acontinuous stirred tank reactor is fed with an ethylene oxide stream, acatalyst stream comprising a

THF solution of a carbonylation catalyst where the catalyst consists ofthe combination of chromium (III) salph complex and carbonyl cobaltate,and a carbon monoxide stream. The reactor is maintained at a temperatureof 60° C. by heating, and maintained at 600 psig by feeding carbonmonoxide on demand to a headspace within the reactor at that pressure.The reaction volume in the reactor is maintained at a constant level bywithdrawing a reaction product stream from the reactor at a mass flowrate corresponding to the sum of the mass flows entering the reactor.The catalyst and EO feeds are maintained at a rate such that thechemical composition of the reactor contents are maintained at a steadystate wherein the reaction mixture contains between 0.2 and 2 weightpercent ethylene oxide, and between 20 and 60 weight percent betapropiolactone. The reaction product stream is directed first to a flashchamber maintained at a reduced pressure (e.g. between about 0.1 and 0.8bar). Volatiles released from the reaction product stream in the flashchamber are recompressed and recycled. The reaction product stream ispumped from the flash chamber and flowed through a packed columncontaining beads of a sodium-form cation exchange resin. The resinexchanges sodium atoms for the cationic Lewis acid in the product streamto provide a first intermediate product stream substantially free of thecationic Lewis acid and containing sodium carbonyl cobaltate. The firstintermediate product stream is fed to a second column containing thechloride form of an anion exchange resin to provide a secondintermediate product stream containing THF, beta propiolactone andsuspended sodium chloride. The second intermediate product stream is fedto a distillation unit where the THF and beta propiolactone arefractionated. The beta propiolactone is carried forward to anotherprocess while the THF is recycled. Solids primarily consisting of sodiumchloride along with small amounts of polymerized products and catalystresidues are disposed of as waste.

The reactor is operated in this way for a first interval of 12 hoursduring which time the two ion exchange columns have accumulated catalystresidues and become substantially saturated with cationic Lewis acid andcarbonyl cobaltate. At this time the saturated columns are removed fromthe reaction product pathway and replaced with fresh columns. Thesaturated exchange columns are treated with brine to elute the catalystcomponents which are extracted into a suitable organic solvent,recombined and purified to provide a new batch of carbonylation catalystwhich is stored and fed to the reactor in a future time interval.Meanwhile, the eluted columns are processed to ready them for return toservice in the process.

In a second example of a process according to the present invention, acontinuous stirred tank reactor is fed with an ethylene oxide stream, acatalyst stream comprising a dioxane solution of tetraphenylporphyrinatoaluminum carbonyl cobaltate, and a carbon monoxide stream. The reactoris maintained at a temperature of 60° C. by heating, and maintained at600 psig by feeding carbon monoxide on demand to a headspace within thereactor at that pressure. The reaction volume in the reactor ismaintained at a constant level by withdrawing a reaction product streamfrom the reactor at a flow rate corresponding to the sum of the flowsentering the reactor. The catalyst and EO feeds are maintained at ratessuch that the chemical composition of the reactor contents aremaintained at a steady state wherein the reaction mixture containsbetween 0.2 and 2 weight percent ethylene oxide, and between 20 and 60weight percent beta propiolactone. The reaction product stream ismaintained under 600 psig of CO pressure and directed through a resincolumn containing the chloride form of an anion exchange resin. Theresin exchanges chloride atoms for the carbonyl cobaltate in the productstream to provide a first intermediate product stream substantially freeof the cobalt carbonyl and containing tetraphenylporphyrinato aluminumchloride. A non-polar high boiling hydrocarbon is injected into thefirst intermediate product stream and the stream is pumped through acombined static mixer and heat exchanger such that it is cooled to asub-ambient temperature and the tetraphenylporphyrinato aluminumchloride precipitates. This stream is fed through a filter unit toaccumulate the solids while the filtrate from this unit is directed to adistillation unit where the dioxane and betapropiolactone are separated.The isolated beta propiolactone is carried forward to another processwhile the dioxane is recycled. The heavies from the distillation unitconsisting primarily of the high boiling hydrocarbon are cooled andrecycled.

The reactor is operated in this way for a first interval of 12 hoursduring which time the anion exchange column accumulates carbonylcobaltate until it is substantially saturated. At this time thesaturated column is removed from the reaction product pathway andreplaced with a fresh anion exchange column. The saturated exchangecolumn is treated with brine to elute sodium carbonyl cobaltate which ispurified and used to generate new carbonylation catalyst by combining itwith chloride salt of the Lewis acid recovered from the filtration unit.The resulting batch of carbonylation catalyst is stored and fed to thereactor during a future time interval. Meanwhile, the eluted anionexchange column is processed to ready it for return to service in theprocess during a future interval.

It is to be understood that the embodiments of the invention hereindescribed are merely illustrative of the application of the principlesof the invention. Reference herein to details of the illustratedembodiments is not intended to limit the scope of the claims, whichthemselves recite those features regarded as essential to the invention.

What is claimed is:
 1. A method for the continuous reaction of anepoxide and carbon monoxide comprising: a) feeding a continuouscarbonylation reactor during a first interval of time with a catalystfeed stream comprising a carbonylation catalyst, where within thereactor, the epoxide and the carbon monoxide react in the presence ofthe carbonylation catalyst to provide a reaction product streamcomprising an epoxide carbonylation product and carbonylation catalystb) treating the reaction product stream; c) separating at least aportion of the carbonylation catalyst from the reaction product stream,wherein the carbonylation catalyst comprises: a cationic Lewis acid andan anionic metal carbonyl; (d) accumulating the cationic Lewis acidseparated in step (c) throughout the first interval of time to obtain acationic Lewis acid batch, and (e) feeding a continuous carbonylationreactor during a second interval of time with a catalyst feed streamwherein at least a portion of the catalyst in the catalyst feed streamis derived from the cationic Lewis acid batch accumulated in step (d).2. The method of claim 1, wherein the epoxide is ethylene oxide.
 3. Themethod of claim 2, wherein the epoxide carbonylation product is selectedfrom the group consisting of: beta propiolactone, succinic anhydride,polypropiolactone, 3-hydroxypropionic acid, and a 3-hydroxypropionateester.
 4. The method of claim 2, wherein the epoxide carbonylationproduct comprises beta propiolactone.
 5. The method of claim 1, whereinstep (c) comprises removing the anionic metal carbonyl from the reactionproduct stream.
 6. The method of claim 1, wherein the carbonylationcatalyst comprises a metal carbonyl compound in combination with one ormore other catalyst components.
 7. The method of claim 6, wherein step(c) comprises selectively removing the anionic metal carbonyl to the atleast partial exclusion of other catalyst components.
 8. The method ofclaim 1, wherein step (c) comprises selectively removing at least aportion of the anionic metal carbonyl compound from the reaction productstream using an anion exchanging material.
 9. The method of claim 1,wherein step (c) comprises selectively removing at least a portion ofthe cationic Lewis acid from the reaction product stream using a cationexchanging material.
 10. The method of claim 1, wherein step (c)comprises treating the reaction product stream using an anion exchangingmaterial to remove the anionic metal carbonyl and separately treatingthe reaction product stream using a cation exchanging material to removethe cationic Lewis acid; and wherein the anionic metal carbonyl removedby the anionic exchanging material is accumulated in step (d).
 11. Themethod of claim 1, comprising a step of regenerating the accumulatedcarbonylation catalyst from step (d) before feeding the cationic Lewisacid in step (e).
 12. The method of claim 11, wherein the step ofregenerating activates the carbonylation catalyst.
 13. The method ofclaim 11, comprising applying pressure and carbon monoxide to thecarbonylation catalyst to regenerate the carbonylation catalyst.
 14. Themethod of claim 11, wherein the anionic metal carbonyl is regenerated bycombining the metal carbonyl with an additional Lewis acid.
 15. Themethod of claim 1, wherein the epoxide is chosen from a group consistingof ethylene oxide, propylene oxide, 1,2-butylen oxide, 2,3-butyleneoxide, epichlorohydrin, cyclohexene oxide, cyclopentene oxide,3,3,3-Trifluoro-1,2-epoxypropane, styrene oxide, a glycidyl ether, and aglycidyl ester.
 16. The method of claim 1, wherein the anionic metalcarbonyl is tetraphenylporphyrinato aluminum carbonyl cobaltate.
 17. Themethod of claim 5, wherein the anionic metal carbonyl is a cobaltcarbonyl compound.
 18. The method of claim 1, wherein the anionic metalcarbonyl is carbonyl cobaltate.
 19. The method of claim 1, furthercomprising: treating the cationic Lewis acid accumulated in step (d) byswapping a non metal carbonyl anion with the anionic metal carbonyl. 20.The method of claim 10, further comprising: treating the cationic Lewisacid accumulated in step (d) by swapping a non metal carbonyl anion withthe anionic metal carbonyl.